2019 UM Molecular & Integrative Physiology Newsletter

PHYSIOLOGY MAT TERS 2019 Mo l e c ul a r & I n te g rat i ve Phys i ol og y

Backyard Brains Neuroscience is often perceived to be too complex or too expansive to be taught in K12 schools. p.4

Contents

Life After Twenty Years as Physiology Chair 8

The Early Years in Physiology at Michigan 21

03

From the Chair

04

Backyard Brains

06

Getting the Grant

10

Battling the Scourge of Aging

14

An Exciting Time to Be APS President

15

MS in Physiology

16

Louis G. D’Alecy Professorship of Physiology

18

Postdoc Experience

19

From One Big Ten Family to Another

20

Summer Undergraduate Experience

22

Scientific Impact

23

PhD Graduates

Editorial Team: Sarah Lawson - Designer Sue Moenter - Editor Santiago Schnell - Editor

Frosty Reception 24

2

Physiology Matters

From the Chair Dear Readers,

W

hen we began to assemble the 2019 edition of Physiology Matters, we could not imagine the world we would be living in when it went to press. As I write this, the number of COVID-19 cases world-wide has crossed one million.

While our research labs are currently ‘ramped-down’ to essential activities, our faculty and trainees have made an astoundingly rapid and successful transition to delivering courses via webbased platforms, ensuring educational continuity. Many of our joint faculty and alumni are on the front lines of the clinical response caring for patients, and our laboratories have contributed with generous donations of personal protective equipment for the hospital. We sincerely hope all members of our extended Physiology Family are safe and well, and remain so through this crisis.

Despite the world situation, there is much to celebrate with the continued development of Physiology at Michigan. We hope this look at the extraordinary activities carried out by our department members over the past year provides you a welcome break.

The department has 110 faculty among primary, joint, research, adjunct and active emeritus tracks, as well as many trainees. There are over 60 postdoctoral fellows, 45 PhD and 31 MS students. Despite the large size of our department, we treasure our informality and unique sense of community.

It is thrilling to enter any of our laboratories or classrooms and sense the intellectual excitement all around us. It grows from our shared passion for physiology, its importance and knowing that we are part of this great enterprise.

Conscious of this, we will continue prioritizing our efforts to remain as one of the top physiology departments in the world through our outstanding research, education and service contributions. In the immediate future, we will be focusing on the well-being of our trainees and faculty, and helping them transition back to full-time, in-person research and education activities. Our near-term philanthropic efforts will focus on two areas. The first will be support for our Physiology Annual Fund, allowing us to direct resources where they are most needed as we emerge from the COVID-19 crisis. The second will be support for the MS and PhD Education Funds, which serve our domestic and international students from all backgrounds working in any area of physiology.

It has been a pleasure to meet so many alumni and friends over the last three years of service as interim department chair. I am delighted to continue sharing the responsibility of guarding our department’s history as well as its future.

Yours faithfully,

Santiago Schnell Interim Chair, Department of Molecular & Integrative Physiology John A. Jacquez Collegiate Professor of Physiology

Physiology Matters

3

Backyard Brains

By Greg Gage Adjunct Assistant Professor, Molecular & Integrative Physiology

4

Physiology Matters

I

am a neuroscientist that has recently joined the Molecular & Integrative Physiology department as an adjunct assistant professor. My work builds upon a background

in neuroethology, engineering, and education in a rather unconventional way.

Neuroscience is often perceived to be too complex or too expansive to be taught in K12 schools. It is not surprising that neuroscience is typically taught only at the university level, and experiments using living brains are typically only found at well-funded research institutions.

Perhaps a better reason why neuroscience doesn’t find its way into more classrooms may not be because the brain is too complex, but rather the research tools are too expensive.

There are a limited number of active neuroscience researchers when compared to typical consumers, so the market that has developed to support them with equipment must charge a premium to stay in business. This is not a problem for wellestablished neuroscientists as they budget for this in their grants, but it makes neuroscience tools out of reach for most high schools and elementary schools.

As a graduate student in the University of Michigan’s psychology department, my labmate (Tim Marzullo) and I spent our summer scheming of a way to change this.

We

created a self-imposed challenge to develop a tool that could record living neurons for less than $100. We presented our working prototypes at a major neuroscience conference, and much to our surprise it was picked up by the journal Nature and soon we were receiving emails from around the world. Other scientists wanted to purchase the invention to demonstrate live neuroscience recordings to their students (and use in their labs too!)

We decided to form a small

company “Backyard Brains,” named in honor of the bugs we used to record living neurons (cockroaches, worms, etc.)

It’s been over a decade since the initial invention, and Backyard Brains has been growing ever since!

We have

developed products for K12 that allow young scientists to perform electrophysiology on neurons (spikes), muscles (EMG), the heart (EKG) and the brain (EEG). We create kits using Arduinos that allow students to build brain-machine interfaces and neuroprosthetics. We allow students to learn about microstimulation by building their own cyborg cockroach: the RoboRoach (It’s still the only commerciallyavailable cyborg to date). Even advanced research topics like optogenetic manipulation of neurons or machine learning of behaviors can be done in the classroom.

I’ve turned an alternative post-doc into an alternative academic career.

Our work is now supported by a mix of

academic grants and product sales. Our research lab consists of undergraduate students and teachers, and our work is published as new lesson plans and peer-reviewed research papers.

So don’t be surprised to overhear 10-year olds

debating Rate-Based vs. Spike-Based theories of the brain!

Physiology Matters

5

Getting the Grant: Meet the Team By: Jane Coffey, Jason Yunk and Annmarie Thomas (as pictured to the right)

A

bstract The University of Michigan Department of Molecular & Integrative Physiology (MIP) is consistently ranked as one of the top basic science departments

in the United States. For fiscal year 2019, MIP was ranked 2nd in the U.S in NIH funding with 72 awarded grants translating to over $22 million in funding. MIP is full of passionate, worldclass scientists seeking fundamental knowledge for greater advancement of human health. A crucial element of our scientists’ success is the pre-award grants team. With approximately 120 proposals submitted annually, they’re an essential component of both getting the grant submitted on time and accurately meeting all UM and Sponsor requirements to increase the chance for success.

Senior/Key Personnel Jane: I have been working at UM for over 25 years, with the majority of that time in research administration. Pre-award is never dull; policies and procedures are constantly changing, and so are the players. The best part of the job is working with so many different types of people from grad students to seasoned faculty. Each brings their own style to the proposal

an R01 or F31, there is deep satisfaction knowing you were

and, when time allows, I enjoy reading to get an inside look

able to contribute to that award. It’s a pleasure to work for

at the science being done in the labs.

Physiology, and to be surrounded by passionate researchers whose aim is to make this world a better place.

Annmarie: I have been a grants administrator for 13 years and the pre-award responsibilities have always been the best

Specific Aims

part of working in research administration. It is a delightful

Our commitment is to serve faculty and ensure our research-

feeling to see grant proposals that I assisted the faculty and

ers are in the best possible position to secure funding. Some

fellows with get awarded. This is a feeling that has not left

of the primary ways we help are by reviewing Funding Oppor-

me over the years in my career, and I am very proud to be

tunity Announcements, providing checklists of all components

a grants administrator with Physiology. You meet so many

and deadlines, building budgets, proofreading & processing

outstanding researchers with brilliant ideas, and seeing this

proposals, submitting Just in Time requests, Research Per-

all come together in the proposals to share with others is re-

formance Progress Report, and essentially any other request.

markable. In the years ahead, my goal is to continue to assist

Our aim is to be a one-stop shop to all things research.

our researchers and to gain a greater appreciation for my team and Department.

We are here to help. From multi-center training grants to independent foundations, we submit a variety of proposals. Our

Jason: I am relatively new to research administration, having

scope of knowledge is wide and we love to see researchers

been in the role for three years. By far, the most rewarding

succeed. The pre-award team is committed to excellence and

part of my job is seeing our scientists get funded. Whether it’s

look forward to continuing our successes together.

6

Physiology Matters

Physiology Matters

7

Life After 20 Years As Physiology Chair:

A Personal Journey

By John Williams Professor Emeritus, Molecular & Integrative Physiology

I

came to the University of Michigan in 1987 as Chair of the Department of Physiology and served close to 21 years.

I enjoyed the challenge and effort of building

the department, recruiting new faculty, continuing an active research program on the exocrine pancreas and teaching physiology. Ultimately we made the transition from classical physiology to more of a focus on cellular and molecular mechanisms

using

transgenic

animals

and

changed

the name of the department to Molecular & Integrative Physiology. After 18 years I felt that the department needed new leadership asked the Dean to step down. This led to a period of remodeling to prepare modern laboratories for a new Chair and their recruits. Also at this time, I began to think of what I would do with my extra time after serving as Chair, as I had no desire to retire.

to continue their education without support for school fees in

Three ideas for new directions occurred and I pursued all three.

The first was to get more involved in medical

education at the University of Michigan and in Africa.

The

second was to start a new form of electronic publication, an online knowledgebase covering the exocrine pancreas that became the Pancreapedia.

The third direction, which

matured later, was to become involved with addressing the oncoming climate crisis. All of this took place while maintaining an

active

research

laboratory

over

the

next

decade.

My interest in medical education in Africa arose at a time when our medical school was expanding its emphasis on improving teaching and learning.

I had been teaching medical and

graduate students for 40 years and felt I understood how it worked, which incidentally proved not to be completely true.

My wife and life partner, Christa and I had been to Tanzania in 2006 and fell in love with the people and the country. She joined a friend in helping to raise money and provide personal support to students, often orphans, who would not be able

8

Physiology Matters

Kenya and Tanzania. Much of her success has been from the person-to-person involvement. As a result, I was ready when Joe Kolars who leads the Global Health Program asked me to help with a new program to send PIBS graduate students to teach basic science in new medical schools in Ethiopia. Lori Isom, the PIBS Director at the time was moving on to become the Chair of Pharmacology so I stepped in as the faculty lead and academic resource person when we sent 12 students to teach for several months in three new medical schools largely staffed by new medical doctors who were fulfilling their national service requirement. Although we also sent a smaller group a year later, the obstacles were greater than expected.

Our students had a great experience and gained confidence in their teaching abilities but had a relatively small effect on solving the overall problems of establishing new schools outside of major population centers. While in Ethiopia, I met the academic and government leaders and learned about medical education at St. Paul’s Millenium Medical School and the University of Addis Ababa. This led to a subsequent

program where five junior basic science faculty from the two

returning to Michigan I started reading and learning how to

schools came to Michigan for six months supported by the

quantitate my carbon footprint. I initiated a study group at

Ministry of Health to work on their PhD degrees. Although

Ann Arbor Friends Meeting of individuals concerned about

the time was predictably too short, I believe all the students

climate change.

benefitted from their experience that would help them with

calculate their carbon footprint and we decided to start a

their careers. Although I considered spending an extended

voluntary carbon tax with the collected funds to help others

time in Ethiopia, I had other work and family issues that

use renewable energy.

required staying in Michigan.

organize book readings. In the spring of 2019, I realized I

This led to a worksheet for individuals to

I also started to give talks and

could contribute my passion, knowledge and organizational The second area I pursued was the Pancreapedia. The idea

skills to help larger groups such as the City of Ann Arbor and

for an on-line open access knowledge base on the exocrine

the University of Michigan. I closely followed the development

pancreas arose at a discussion with colleagues at the Gordon

of the University of Michigans’s President’s Commission on

Conference on Exocrine Glands about ten years ago.

I

Carbon Neutrality and joined a local university group that

drew up an ambitious model for content and got help as a

became Voices for Carbon Neutrality whose mission is to

group class project from graduate students in the School of

help push and guide the urgency of University of Michigans’s

Information to design a prototype using Drupal as a content

efforts. As part of this effort, I helped a group of our medical

management system.

I wrote some entries and was able

students to get together as an organized Climate group and am

to get the University Library to invest in programming an

now working similarly with graduate students and postdocs.

improved and more robust site. I recruited an international

When the President’s Commission on Carbon Neutrality chose

team of Editors and Editorial Board members and the

to set up eight Internal Action Teams to delve deeply into

American Pancreatic Association agreed to provide financial

specific areas, I volunteered and was chosen as Co-Faculty

support for hiring a student as Content Manager. I handle

Lead for the team working on University Travel. We recruited

the solicitation and review of manuscripts as well as copy

six graduate and undergraduate students from diverse areas

editing. Later, I obtained a grant from the National Library

who are currently quantitating the scope, mode and carbon

of Medicine.

You can see the result at www.pancreapedia.

footprint of the University of Michigan travel. We expect to

com. Two years ago we published a 600-page reference book

provide recommendations on how to reduce travel, replace

on Pancreatitis, which is free online although you can buy a

some with other forms of communications and when possible

paper copy from Amazon which uses print on demand. The

reduce the travel footprint. Finally, we are investigating how

site has widespread use by younger scientists or individuals

offsets could be used to mitigate the effects of travel so that

new to the pancreas field, particularly for its Methods section.

travelers and their fund source could cover the full cost of the

The current challenge is to ensure its continuation after my

effects of the travel on the climate.

efforts end, most likely by having a publishing company with a pancreas journal take it over.

On January 1, 2020, my title changed to Emeritus Professor of Physiology. However, I have so much useful work still going

My third area of interest deals with the looming climate crisis.

on that I continue with the daily pursuit of my professional

I have always been an outdoors person and take pleasure

passions. I am thankful to our department for allowing me

and have support from observing the natural world. However,

to keep my office and the Medical School for allowing me to

I grew more aware of anthropogenic climate change and at

continue to teach Gastrointestinal science. I hope to continue

one point about eight years ago flying back from our annual

this and my other projects along with longer but fewer trips to

summer trip to Washington state, I was meditating on my

Washington to enjoy our beach house on Samish Island just

personal responsibility for greenhouse as production. Upon

south of Bellingham.

Physiology Matters

9

Battling the Scourge of Aging

F

or over half of a century, the Department of Molecular & Integrative Physiology (MIP) has partnered with the Geriatrics Center, the Division of Geriatric and Palliative Medicine, and the Institute of Gerontology to develop research and clinical

communities devoted to defeating the evils of aging and the many forms that it may take. The faculty at the University of Michigan (UM) are now recognized as one of the finest in the world, for the study of the Biology of Aging. Consistently ranked in the top ten in research funding from the National Institute on Aging and in the quality of its primary care, UM is also home to several prestigious national centers and programs including the Paul F. Glenn Center for Aging Research, the Claude D. Pepper Older Americans Independence Center, and the NIH-funded Career Training in the Biology of Aging program, which, for the past 35 years, has trained national leaders in aging research, medicine, and policy.

Nine primary MIP faculty members also hold appointments in the Geriatrics Center because major components of their research portfolios are devoted to unraveling the mysteries of aging. Recognizing that the complexity of aging is such that it is a foe that no single researcher can withstand, this closeknit, collaborative group loosed their superior intellect and unrivaled energy on understanding the basic mechanisms of aging and age-related disease. In 2019, the accomplishments of UM’s mightiest aging researchers, the Aging Avengers, have been featured in publications, conferences, classrooms, and public gatherings around the country.

The Aging Avengers’ achievements in this space are auspicious, as public and private interest in aging research is growing. The importance of aging as a risk factor for many diseases is now recognized across Institutes within the NIH. Industry is also taking notice. Well-established pharmaceutical companies, such as GSK and Novartis, have created new divisions focused on aging biology, and well-financed start-ups, often supported by highly-attractive parent companies (e.g., Calico-Google), are capturing the attention of the brightest young scientists.

Dr. Sue “She-Hulk” Brooks is interested in eliminating the breakdown of muscle function, termed sarcopenia, that occurs with advancing age. Drs. Myungjin “Captain Marvel” Kim, Jun Hee “Quicksilver” Lee, and Matthias “Thor” Truttman seek to better understand how our body’s innate stress responses can be co-opted to combat metabolic dysfunction, prevent the aggregation of mis-folded proteins, and extend healthy

lifespan. Drs. Christi “The Wasp” Gendron, Scott “Mr. Fantastic” Leiser, Shawn “Vision” Xu, and Scott “Iron Man” Pletcher share interests in the role of the brain in controlling aging, at least in part through its ability to detect and respond to environmental conditions through sensory systems.

10

Physiology Matters

Together, we can all be comfortable in knowing that these super-scientists are working tirelessly to slow the pace of aging and to improve health at older ages, so that our children and all future generations are able to enjoy long, healthy lives.

Dr. Sue “She-Hulk” Brooks Despite clear success in rapidly building and maintaining muscle mass, She-Hulk recognizes that even super-heroes risk wasting and weakness during aging owing to the age-associated denervation and muscle fiber loss that appears inescapable. For normal people, gamma radiation is ineffective at promoting muscle health, so instead Dr. Brooks’ research targets the neuromuscular junction (NMJ), which is where motor neurons and muscle cells come together and where the signaling between them occurs that drives muscle movement. It turns out that large numbers of NMJs display structural abnormalities in old animals and old people, and these anomalies are observed in both the motor neurons, including increased branching and swelling, and at the muscle fiber membrane where dispersal of the receptors

that receive neuronal signals

occurs. In addition, with aging, substantial numbers of NMJs accumulate that have lost the critical overlap between the motor neurons and muscle membrane receptors. Whether motor neurons themselves are lost with age remains a controversial topic in the field, but progressive denervation is consistently seen late in life in rodents and humans, contributing to muscle weakness and muscle fiber loss.

In 2019, Dr. Brooks’ group focused on determining whether the critical events that initiate NMJ degeneration are happening in the neurons or in the muscle. Their group created genetically engineered mice in which the balance of reactive oxygen species, which can trigger oxidative stress that influences many biological processes, was altered specifically in either the motor neurons or muscle cells of the NMJ. They discovered that altered redox homeostasis in motor neurons triggers NMJ degeneration but alone is not sufficient to cause complete denervation. They also discovered that muscles of old animals are more likely than young muscles to be injured during normal contractions and that, following injury, regeneration is impaired. Dr. Brooks is currently testing the hypothesis that age-related muscle fiber denervation results from a breakdown in the remodeling of NMJs that occurs throughout the lifespan and whether this is compounded by cycles of injury and incomplete repair.

Drs. Christi “The Wasp” Gendron and Scott “Iron Man” Pletcher Like many of their superhero colleagues, Drs. Gendron and Pletcher recognize the power of sensory systems. Although we may intuitively appreciate that certain sensory experiences could be accompanied by deeper biological changes—the “fight or flight” response is triggered by the sense of danger and characterized by many physiological changes—Drs. Gendron and Pletcher have identified critical sensory structures and their functions that impact the aging process itself. By developing new technology to monitor neuron activity and behavior in fruit flies, they have shown that sensory neurons relate information about nutrition, danger, and conspecifics to initiate rapid changes health and aging. For example, exposure of Drosophila to the smell of food limits the beneficial effects of dietary restriction, while activation of “hunger” neurons mimics many effects of dietary restriction, including an increase in lifespan. Furthermore, the loss of specific neurons that mediate smell and taste also increase fly lifespan and physiology and influence measures of healthy aging, including sleep and daily activity patterns, and mere perception of the opposite sex modulates lifespan through neural circuits that establish motivation and reward. Ongoing studies indicate similar effects in mice.

In 2019, The Wasp and Tony Stark published their discovery that fruit flies exhibit significant changes in physiology and aging in response to the recognition of dead individuals in their environment. They pinpointed sight as the primary sensory mechanism through which this occurs, and they identified metabolomic changes in the brain as a result of the perceptive experience. The effects that they observed in flies are remarkably consistent with similar effects

reported to be associated with psychological stress in humans, and they were reversed when flies were fed

human drugs that target serotonin signaling. These results indicate deeply conserved mechanistic links between psychological and physical health, and they identify a candidate neural aging pathway through which the consequences of psychological effects manifest in humans.

Physiology Matters

11

Dr. Scott “Mr. Fantastic” Leiser

Like their natural ally, the Pletcher lab/Stark Industries, the Leiser lab is interested in how perception of the environment affects animal physiology. However, unlike our collaborating friends, they take a multi-organism and multi-system approach to aging research. By studying the roundworm Caenorhabditis elegans, they use large-scale screens and genetic engineering to manipulate animals and understand genes and processes that are important for promoting health and longevity. They then study conserved genes of interest in cell culture models, looking for conserved function of the genes in cellular processes. Finally, they use studies in mice to validate questions pertaining to the importance of genes, drugs, and/or biological processes that affect aging. Importantly, their research is not unidirectional, meaning that they

seek to translate findings across organisms, making their data much more likely to be applicable to

people.

In 2019, their nascent laboratory focused their investigative powers on the perception and response to stress and how this response relates to changes in healthspan and longevity. In the course of this work, Mr. Fantastic and colleagues mapped key circuits that control how animals sense food and oxygen and how they react to deprivation of these key metabolic components.

These studies, as yet unpublished, revealed that both serotonin and dopamine signaling are crucial for one or both of these responses, and that there are drugs available with the potential to mimic life-extending interventions like dietary restriction.

Dr. Lesier’s group also observed that the key changes in these stresses involve changes in proteins that control metabolism, providing a distinct mechanism for slowing the ravages of aging. As they continue to develop an understanding of both the perception and physiological changes that are associated with stress, the human race will inch ever closer to the development of future treatments that extend health and lifespan.

Drs. Myungjin “Captain Marvel” Kim and Jun Hee “Quicksilver” Lee Superheroes are always under stress to save the world. Too much stress is bad, but a little can be good, as it can help us focus on keeping everybody safe. It is the same for for normal humans.

At the cellular level, too much environmental stress can be damaging to cells and tissues; however, a little bit of stress is known to activate adaptive mechanisms that prevent further stress-induced damage and that repair existing damage. It should be noted that fortifying these mechanisms not only improves stress resistance but also extends the health- and lifespan of an organism. Drs. Kim and Lee investigate these stress response mechanisms with the hopes of discovering new ways to tackle aging and to promote health and productivity later in life.

Specific types of everyday stress, such as that induced by endurance exercise, can also be beneficial for an organism’s health. Despite extensive studies, however, the molecular mechanisms underlying the benefits of exercise have remained elusive. Several recent studies indicated that exercise induces synthesis of a protein family named Sestrins. More recently, Captain Marvel and Quicksilver and their colleagues used experiments conducted in the fruit fly and the mouse to discover that a family or proteins, called Sestrins, are both necessary and sufficient for the metabolic benefits of exercise. Sestrin-deficient animals did not exhibit increases in endurance and metabolic fitness following exercise, while animals in which Sestrin was overexpressed experienced the metabolic benefits of exercise in the absence of exercise itself.

Further research is currently being undertaken to identify how Sestrins are regulated and to

identify drugs that may modulate their activity.

Dr. Matthias “Thor” Truttmann

Dr. Truttmann and his laboratory study how a specific class of proteins, called molecular chaperones, control protein aggregation in the context of neurodegeneration and aging. In the past, Dr. Truttmann has used S. cerevisiae (Brewer’s Yeast) and C. elegans (a nematode worm) models in combination with biochemical approaches to define the impact of how a specific modification that is applied to proteins after they are formed, called AMPylation, modulates chaperone activity. He showed that increasing chaperone AMPylation alters the aggregation dynamics of disease-associated proteins such as amyloid beta and a-synuclein, two

12

Physiology Matters

proteins linked to the pathology of Alzheimer’s disease and Parkinson’s disease, respectively. Recent work indicates that these processes are conserved from worms to humans and may indeed impact protein aggregation in disease patients. Indeed, Dr. Truttmann believes that chaperones may be prime targets to intervene in and to control aging-associated protein aggregation processes.

Thor, who was granted his alter-ego because of his scientific training in the cold mountains of northern Europe, was the most recent hire of the Department of Molecular and Integrative Physiology. Since summer 2018, Thor has been swinging his hammer in Ann Arbor and has been devoted to recruiting a strong team to help him continue his scientific adventures, which focus on the crossroads between chaperone function, protein aggregation, and aging. Together with his team of super-women and -men, Thor established his new refugium, where he retreats to and discusses his newest scientific plans with his team members. It’s only a matter of time before their mighty work will be unveiled to the public and the man with the hammer returns.

Dr. Shawn “Vision” Xu As suggested by his moniker, Vision is interested in understanding how animals sense their external and internal world through sensory systems. Sensory cues, such as temperature, chemicals (odor and tastent), touch and light regulate not only an animal’s behavior, but also its physiology — such as aging and longevity. For example, both cold- and warm-blooded animals live longer at lower body temperatures, highlighting a general role of temperature in lifespan regulation. However, the underlying mechanisms remain largely unknown. Dr. Xu’s lab recently identified a cold-sensitive thermal sensor that detects temperature decreases in the environment to extend lifespan, demonstrating that genes actively promote longevity at cold temperatures. This calls into question the century-old view that cold-dependent lifespan extension is simply a passive thermodynamic process.

Vision’s laboratory is now identifying new

genes and pathways that mediate temperature- and chemical cue-dependent regulation of lifespan and healthspan in C. elegans. Ultimately, they would like to derive a thorough understanding of how sensory cues regulate aging and longevity.

Like Dr. Sue “She-Hulk” Brooks, Dr. Xu is also interested in understanding the mechanism of motor aging. As animals and humans age, the motor system undergoes a progressive functional decline, leading to frailty. Age-dependent functional deterioration at neuromuscular junctions (NMJs) contribute to this frailty. However, it is unclear whether one can intervene in this process to slow motor aging. In work published in 2019, Dr. Xu’s group reported that genetic ablation of a gene called SLO-1, which encodes a channel that normally functions to suppress the function of motor neurons, reduced the rate of agedependent motor activity decline and, surprisingly, extended nematode lifespan. Their results demonstrate that genetic and pharmacological interventions in the aging motor nervous system can promote both healthspan and lifespan.

Dr. Geoff “Dr. Strange” Murphy Dr. Strange and his lab study learning and memory. Specifically, the Murphy Lab is interested in a brain region known as the hippocampus; which is required for the encoding of long-term memories. Similar to the Time Stone within the Eye of Agamotto, the hippocampus allows humans to travel through time. If the hippocampus is damaged or becomes dysfunctional, humans lose the ability to encode new memories of people places and events, thus confining them to the present—which inevitably becomes the past. Dr. Murphy and his team are working to better understand how the hippocampus promotes the storage of long-term memories and how this process is disrupted during aging and in Alzheimer’s disease. The Murphy lab has recently genetically engineered a transgenic mouse which mimics the age-related increase in expression of an

L-type calcium channel known as CaV1.3. Young CaV1.3 transgenic mice exhibit cognitive impairments

and dysregulated neuronal calcium homeostasis, like that typically observed in aged mice. In collaboration with Daniel Lawrence in MIP, the Murphy lab is also working to better understand the cause of cerebrovascular derangements that are associated with Alzheimer’s disease and how the altered vasculature impacts neuronal function and cognition. Using a transgenic mouse model that expresses mutated proteins known to be altered in Alzheimer’s disease, the lab has developed a method for visualizing the entire brain vasculature which allows them to quantify blood vessel morphometry with ~1-micron resolution. Using this data, the team can mathematically model the changes in cerebral blood flow. The long-term goal is to develop drugs designed to ameliorate Alzheimer’s disease related vascular dysfunction.

Physiology Matters

13

An Exciting Time to be APS President

By Linda Samuelson John A. Williams Collegiate Professor of Gastrointestinal Physiology

I

t is a great honor to have been elected as the 93rd president of the American Physiological Society (APS). Currently, as President-elect, I am part of the executive

leadership team with the President and the Past-President. I transition to my term as President at the APS annual meeting at Experimental Biology in April 2020.

It is especially meaningful for me to be following in the footsteps of my mentor and colleague John A. Williams, who was the 76th APS president. Michigan Physiology has had a remarkable impact on the APS since its inception in 1887. I will be the 11th member of our department to serve as APS President. Two of these people, W.H. Howell and Warren P Lombard, were founding members of the APS. I am honored to be joining this distinguished group of Michigan Physiologists: •

W. H. Howell, Chair and Professor of Physiology

(1889-1892), and APS President (1905-1910).

new initiatives include a revamp of our brand and logo, cre-

•

ating a new APS postdoctoral fellowship program, launching a

Warren P. Lombard, Chair and Professor of Physiolo-

gy (1892-1932), and APS President (1919-1920).

new journal, and completely overhauling the annual meeting.

•

Thus, there are many new things to work on.

Carl J. Wiggers, Instructor of Physiology (1906-

1911), and APS President in 1949.

•

Ralph W. Gerard, Professor of Physiology (1955-

The new journal Function will provide an open-access, multi-

1969), and APS President in 1951

disciplinary home for high-profile publication in the physio-

•

logical sciences. Work is underway to launch the journal in

Horace W. Davenport, Chair and Professor of Physiol-

ogy (1956-1979), and APS President in 1961.

2020. I hope that you will consider sending your best work to

•

this journal, which is designed to promote major insights into

John M. Brookhart, Graduate Student in Physiology

(1935-1940), and APS President in 1965.

•

biological function and disease.

David F. Bohr, Professor of Physiology (1948-1985),

and APS President in 1978.

Perhaps the most exciting but daunting task ahead for the

•

APS is the creation of a new annual meeting. We will part

Harvey Sparks, Professor of Physiology (1967-1978),

and APS President in 1987.

ways with Experimental Biology and put on our own meeting

•

in 2023. The APS staff, leadership team and key members

James A. Schafer, Graduate Student in Physiology

(1963-1968), and APS President in 1996

are currently working to design a new, world-class meeting.

•

The vision is to build an innovative platform that will attract

John A. Williams, Chair (1987-2008) and Professor of

Physiology (1987-present). APS President in 2003.

a broad group of scientists to present their new discoveries.

This is clearly the initiative where my work as APS President

This is a time of great change in the APS. I am deeply hum-

will have the greatest impact.

bled by the task ahead as the APS undergoes a major redesign aimed to position our members and the discipline of

I am excited to be APS President with the Society embarking

physiology at the forefront of scientific discovery. It has been

on so many new things. My term will be filled with new ideas

an exciting time to build from our past and reshape a soci-

and initiatives to build on the past to continue the impact of

ety that has been in operation for 132 years! Some of the

the APS into the future.

14

Physiology Matters

Master of Science in Physiology

By Amy Oakley Director, MS Program and Lecturer, Molecular & Integrative Physiology

I

am honored to serve as the new Director of the MS Program in Physiology, now in its ninth year. We are exceedingly proud of our present cohort and the ongoing success

of our former students. Our team’s goal is to maintain and continue to improve the experience of our cohort both inside and outside the classroom. With our small class size (31 students matriculated Fall 2019), we are able to preserve the collegial and familial feel that I experienced as a PhD student in

(ABRCMS), where she mentors and advises undergraduate

the department. This year’s cohort bonded very early and has

and graduate underrepresented scientists, and at the 2019

organized social events such as a crochet tutorial, intramural

meeting, co-led a workshop on Science Communication.

sports, a yoga session led by an alumna registered yoga instructor, a trip to Cedar Point, coordinating onesie Halloween

In her role as Associate Director of the MS Program in Physi-

costumes, “Friendsgiving,” a Super Bowl viewing party, and

ology, she is able to fully explore and develop those interests

a recent ski trip up north. Lest you think they are all play

in teaching and mentoring through working with the talented

and no work, our students impress us with their hard work

students who make up the MS program cohorts. Isola serves

ethic and service to community. Our Coordinator of Advising,

as co-Course Director for PHYSIOL 592: Integrated Neurosci-

Peggy Zitek, continues to work on our student’s personal and

ence, PHYSIOL 610: Translational and Pathophysiology, and

professional writing development, health professions school

PHYSIOL 605: Professional Development Seminar. Along with

application content, and mock interviews. We are excited to

the rest of the program staff, she helps to advise the MS

welcome to the team the new Program Administrator, Folaké

students through development of their end-of-year capstone

Graves, and the new Associate Director, Dr. Isola Brown, who

papers and presentations, and in deciding their next steps

both hit the ground running, bringing fresh perspectives and

after completion of the program.

contributions to the M.S. Program team.

Outside of work, Isola enjoys traveling (to warmer places), Isola Brown, Ph.D. joined the MS Program in Physiology as

testing her patience with jigsaw puzzles, and running out-

Associate Program Director in October 2019. Isola earned

doors (when we finally get summer in Michigan). Isola has

her Ph.D. in Pharmacology and Toxicology at Michigan State

been warmly welcomed by the rest of the MS Program staff,

University in 2017, where she worked in the lab of Dr. Brian

and the wider department, and has thoroughly enjoyed her

Gulbransen. Isola’s graduate work focused on the role of en-

first few months as a Wolverine.

teric glial cells in regulating inflammation, oxidative stress, and motility, within the gastrointestinal tract. She then com-

Folaké Graves holds an MA in Education degree from the Uni-

pleted a Ford Foundation-funded Postdoctoral Fellowship with

versity of Illinois, Urbana-Champaign. Her professional career

Dr. Brant Isakson at the University of Virginia, studying the

has always involved working with diverse student populations

role of vascular endothelial cells in the pathology of viral in-

at two- and four-year institutes. She enjoys being immersed

fections, before returning to Michigan to join the MS Program

in the educational and cultural hub at the University of Mich-

and MIP.

igan, where she has 13 years of student advising experience in LSA. In her new role in the Department of Physiology as

Throughout her academic and professional career, Isola has

of May 2019, Folaké’s responsibilities include administrative

always had a passion for, and been drawn towards, student

functions, student support, and curricular coordination. She

teaching, outreach, and mentoring. As a graduate student

resides in Ann Arbor with her husband, who received his Ph.D.

and postdoc, she developed outreach activities for young

at the University of Michigan’s Cellular & Molecular Biology

scientists through the MSU Chapter of the Graduate Wom-

Department (PIBS alum), and two teen daughters. In her

en in Science, and the American Physiological Society, and

spare time, Folaké enjoys spending time with her family and

was a guest lecturer for multiple undergraduates and grad-

loves to travel. She looks forward to building relationships

uate pharmacology and physiology courses. One of her fa-

with staff and faculty within the Physiology department in or-

vorite activities outside of the classroom is attending the An-

der to provide students with the best service and educational

nual Biomedical Research Conference for Minority Students

experience during their time at the University.

Physiology Matters

15

Louis G. D’Alecy Professorship of Physiology Louis G. D’Alecy, D.M.D., Ph.D., was born in 1941 on Staten Island, New York City, attended Seton Hall University, earned a D.M.D. in 1966 from New Jersey College of Medicine and Dentistry, and then earned a Ph.D. in 1971 in Physiology at the University of Pennsylvania Medical School. After a postdoctoral fellowship, he was appointed Assistant Professor in the Department of Physiology and Biophysics at the University of Washington School of Medicine. In 1973 he accepted a position as Assistant Professor of Physiology at the University of Michigan Medical School at the request of Professor Horace Davenport. In 1979-1980 he took a sabbatical as a Visiting Associate Professor of Medicine at Harvard University. At Michigan, he rose through the ranks to Professor of Physiology in 1983. From 1985 through 2006 he also held a joint appointment in the Department of Surgery. He retired from his active faculty status on December 14, 2016, and is currently an Active Professor Emeritus of Physiology. time undergraduate and medical student research internships At Michigan, Professor D’Alecy has had diverse academic

all of which enriched and colored his formal classroom teaching

accomplishments in education, research, and service. In

and electrified his scientific work on an eclectic variety of

1973, he began by offering a team-taught course in human

collaborative basic science physiology investigations.

physiology with Professor Matthew Kluger. By 1979 this course was enrolling over 300 students a year and drawing

His doctoral dissertation, under Professor Eric O. Feigl,

from the Dental school, Graduate Nursing and Pharmacy

identified

schools. He transitioned to teaching the undergraduate

blood flow to the brain. At Michigan, the American Heart

Honors Program and the Interflex Program and eventually to

Association awarded him with Grants-in-Aid and then a five-

a growing role in directing and teaching in the Medical School

year Established Investigatorship award. Funding from the

sequences for cardiovascular and respiratory physiology.

National Institutes of Health and numerous pharmaceutical

This last assignment spanned over 36 years from 1981 to

companies contributed to our understanding of the functioning

his retirement in 2017. He received multiple teaching awards

and pathophysiology of the cardiovascular and respiratory

including the Kaiser Permanente Award for Excellence in

systems. Early career collaborations with Professor Kluger

Preclinical Teaching -- which he received several times -- and

identified the role of nasal versus tracheal airflow in the

the Endowment for the Basic Sciences (EBS) teaching Award

control of deep brain temperature in rabbits. Perhaps the

in Physiology. In 2014, he received the prestigious Lifetime

most frequently cited paper with Professor Kluger was the

Achievement Award in Medical Education.

seminal study in birds that established, for the first time, the

sympathetic

and

parasympathetic

control

of

existence, and evolutionary significance of the fever response Beyond the classroom Professor D’Alecy played a substantial

which led to our current understanding of the widespread

teaching role in his research laboratory, which included 45

adaptive and protective value of fever in the body’s response

memberships in doctoral thesis committees and the mentoring

to trauma and infection.

of 11 postdoctoral trainees. He hosted 18 graduate research rotations, 13 undergraduate honors theses, and over 80 part-

16

Physiology Matters

Virtually all of the 140 published research studies from the

D’Alecy laboratory had, if not first authorships, major co-

Committee on Appointments, Promotions, and Tenure and

authorships, by one or more students ranging from high school

two terms on the Medical School Executive Committee, and

students to undergraduates, to graduate students, to medical

multiple terms on the Basic Science Academic Review Board

students, to postdoctoral fellows, and to professional research

for Medical Students. At the University level, he served as

technicians that were routinely involved in all projects. They

Chair of the Senate Advisory Committee on University Affairs

all were trained to record what they saw and not what they

and Chair of the Senate Assembly and Chair of the Faculty

thought. Professor D’Alecy views his role in the research

Senate. He was also motivated to take a pivotal role in the

enterprise to be one of listening to the student, colleague, or

work of the “Joint Faculty-Administration Review Committee

collaborator and teasing out testable hypotheses from their

for the Faculty Grievance Process” resulting in a widely

innocent questions thus developing scientific explorations

used roadmap for resolution of faculty grievances. For these

of the underlying physiological and or pathophysiological

extensive University services, Professor D’Alecy was awarded

significance. Many of the projects addressed inadequate

the Distinguished Faculty Governance Award in 2004.

oxygen supply (hypoxia), or inadequate blood flow (ischemia), to tissues, organs, or the organism under study. Highlighting

Professor D’Alecy has been married to his wife Susan since

the student/faculty collaborative ethos and nature of work in

1964. Together they have three sons, Anthony, Stephen, and

the D’Alecy laboratory is Professor Jeffrey Kirsch who is here

Louis, and five grandchildren, and all still live in the immediate

one of the major donors for the Louis G. D’Alecy Collegiate

Ann Arbor area.

Professorship in Physiologytoday. As a freshman undergrad, Jeff Prof. Kirsch wondered if alterations in the type or amount

Upon learning about the establishment of the collegiate

of metabolic substrate available for energy production could

professorship, Professor D’Alecy said: “I am greatly humbled

increase survival time during hypoxia. A series of collaborative

that my friends and colleagues have honored my contributions

publications demonstrated that elevating blood ketones by

to physiology and the University of Michigan with this endowed

virtually any means increased survival time in an individual

chair…”

exposed to hypoxia. By the time he graduated from medical school, Professor Kirsch had published seven first-authored

The Louis G. D’Alecy Collegiate Professorship in Physiology

papers. Professor D’Alecy reports that he is very proud to

will be awarded to a distinguished member of our faculty, or

have participated in their training of Prof Kirsch and many

to recruit an exceptional individual to join our faculty. The

other students in his laboratory.

collegiate professorship will provide annual discretionary research support that can be used for innovative, high-risk

Professor D’Alecy’s committee and administrative services to

research projects.

the University have been widely recognized. His roles in elected faculty governance included multiple terms on the Advisory

Physiology Matters

17

Postdoc Experience

By Charlotte Vanacker Postdoctoral Fellow, Molecular & Integrative Physiology

I

t has been more than 3 years since I first set foot in the US, here in Ann Arbor, to start working as a postdoctoral fellow in the Department of Molecular & Integrative

Physiology (MIP). While joining the research team of Sue Moenter, I rapidly realized that I was integrating into a much bigger entity: the physiology community. Our department brings together experts, leaders and trainees of very diverse scientific backgrounds. The constant interaction among teams occurring through our monthly MIP seminars, celebratory luncheons, barbecues, and numerous events helps establish strong connections among members and offers a collegial and scientifically rich environment, in which to develop as a young scientist.

MIP recognizes the importance of helping trainees access the tools to build a strong foundation that will allow us to move our careers forward. MIP is particularly supportive of postdocs

Postdocs are also invited to meet with every invited speaker,

in this regard at every step of the postdoctoral journey.

encouraging communication, interaction and networking.

One of the most valuable opportunities I have had has

The environment for postdocs within MIP offers a combination

been volunteering as an instructor for the PHYSIOLOGY

of research excellence and career-building that supports

415 (Laboratory Techniques in Biomedical Research) class

trainee development regardless of career path. It is partly

for Master’s degree and undergraduate students. This

through MIP that I discovered ways in which my skills and

successful experience was set up four years ago by Yatrik

interests extend beyond my ability to conduct scientific

Shah and Nupur Das and provides an opportunity for every

research. I am actively advocating for postdocs by being part

postdoc to participate in designing and teaching lectures and

of the University of Michigan Postdoctoral Association and it

lab courses. I am particularly happy to participate for the

is one of my aims to promote collaboration among postdocs

third time to this course that is updated annually to fit the

in MIP and beyond. I encourage postdocs to join us during

area of expertise of the new instructors. MIP also provides

our newly established monthly Physiology Postdoc Coffee

unique opportunities to participate in outreach activities, for

hour, which will be soon accompanied by a “Postdoc Corner”

example in the Science Education and Engagement for Kids

that will allow us to practice talks, prepare for interviews and

program that introduces science through hands-on activities

provide general peer support. Being a postdoc in MIP helped

in local elementary schools. Importantly, the postdocs and

me understand what I want to become. Is the destination

research investigators of the MIP are represented by our

more important than the journey? A postdoc is a transitional

Physiology Postdoctoral Association, which supports career

and training position and it is crucial to make the best of this

development

by

experience. It is my wish to see an increase in the involvement

postdocs and by inviting faculty to talk about career options

by

organizing

monthly

presentations

in our postdoc community. I want to take advantage of this

including typical academic path and other career paths, like

note to thank the people of our department that makes this

biotechnology, government, pharmaceutical industry and

journey possible, especially Michele Boggs, Angie Tucker,

entrepreneurship. Postdocs that are closer to searching

Rachel Anderson, Heather MacFarland, Sarah Lawson, Lori

for jobs can find unique opportunities by participating in

Meggit, Yatrik Shah, and the whole MIP administrative office

recruitment seminars and chalk talks organized by the

for brainstorming ideas and organizing the MIP life.

department during interviews. This is particularly useful to help us to prepare for this step of our career. Students and

18

Physiology Matters

S

antiago asked me share my new role at Rutgers and comment on the postdoctoral fund carrying my name that Molecular & Integrative Physiology (MIP) kindly

established. I moved to Rutgers University late August 2019 but my ties to and warm sentiments toward Michigan are as strong as ever. I thank MIP and the Department of Medicine (Division of Gastroenterology and Hepatology) for adjunct appointments to help maintain close connections. I am also ceaselessly grateful to MIP for establishing the postdoc fund and wish to thank all who have and continue to contribute to it. In 2017, when MIP first wanted to establish this fund, I was hesitant. But MIP persisted and after I moved to Rutgers, I agreed given the change in my position, and the recognition

by MIP faculty of the need to bolster career development of MIP postdoctoral fellows. The fund, one of the first dedicated endowments at University of Michigan (UM) for postdoctoral fellows, now has a solid foundation that can be used for the benefit of MIP postdocs. MIP took the lead in recognizing the importance of taking specific measures to further postdoctoral career development and established the MIP postdoc program, which became a model for the entire UM medical school, resulting in broader recognition of the need to support these trainees. The efforts by MIP and the medical school

From One Big Ten Family to Another

By Bishr Omary Adjunct Professor, Molecular & Integrative Physiology; Internal Medicine, Div. of Gastroenterology

were highlighted in a commentary published in J Physiology (Enhancing career development of postdoctoral trainees: Act locally and beyond, Vol 597, pp 2317-2322, 2019), coauthored by Santiago, Yatrik, and me along with Drs. Subrama-

This campus was created when the former University of Med-

nian, Swanson, and O’Riordan.

icine and Dentistry of New Jersey joined Rutgers in 2013.

One major strength that New Jersey offers is the diversity of

While at UM (2008-2019), I had the privilege to work on be-

its population; 1 in 5 inhabitants of NJ were born outside the

half of MIP with department chairs, center directors and di-

USA. More than 40% of NJ’s population receives its healthcare

vision chiefs across the medical school. I wish to specifically

from the Barnabas Health System that has partnered with

thank the units that provided essential and generous contri-

Rutgers; this in turn provides exceptional opportunities for

butions totaling $200,000 to jump-start this postdoc fund:

carrying out clinical and translational research. My current ac-

Endowment for the Basic Sciences; the Departments of In-

tivities involve overseeing several Health System-wide efforts

ternal Medicine, Anesthesiology, Cardiac Surgery, Pathology;

including a strategic plan, a research initiative similar to U-M’s

Neurology, Obstetrics and Gynecology; the Department of

Biosciences Initiative, and an awards recognition program. I

Internal Medicine Divisions of Gastroenterology and Hepatol-

am also involved in assessing research cores, minimizing ad-

ogy, Geriatric and Palliative Medicine, and Nephrology; the

ministrative research burdens, and coordinating partnerships

Cardiovascular Center and of course MIP. This Physiology

with entities outside Rutgers, among other efforts. The expe-

Postdoctoral Awards & Symposium Fund supports postdoc-

riences I had at Michigan have been a tremendous help.

toral recognition given at an annual symposium featuring a named lectureship, postdoc travel and small grants, and other

I recently had the pleasure to join MIPs January 30, 2020 cel-

postdoctoral career development activities.

ebration for Liangyou Rui and Yatrik Shah as inductees of the Lou D’Alecy and Horace Davenport professorships, respec-

At Rutgers, I serve as senior vice chancellor for academic

tively. That event reminded me of the supportive family-like

affairs and research for the health sciences campus. Rutgers

environment and collegiality MIP provides for its faculty, stu-

reminds me a lot of the U-M in terms of its size and breadth;

dents, postdocs and staff. MIPs individual parts are enviable,

there are over 150 undergraduate majors and 400 graduate

but the sum of its parts is truly one-of-a-kind. I am grateful

degrees within 29 schools and colleges, with a total enroll-

and honored beyond words for the privilege of having been

ment of over 70,000. Rutgers was chartered in 1766 and is

and continuing to be a member of MIP and the Department

the 8th oldest college in the US. It is now a member of the Big

of Medicine, and I thank you and all the generous donors

Ten. One unique aspect at Rutgers is that all the health-re-

for supporting MIP’s Postdoctoral Awards & Symposium Fund

lated schools (Dental, Health Professions, Medical, Nursing,

that I hope will reach its target goal of $300,000. Although

Pharmacy, Public Health) reside in one virtual campus under

I moved, I have not left and I’ll continue to do my best to

one administrative umbrella that allows them to collaborate.

serve!

Physiology Matters

19

Summer Undergraduate Experience

By William Martinson

I

n summer 2017, I was fortunate to do research at the University of Michigan as part of the Frankel Cardiovascular Center Summer Undergraduate Research Fellowship

(FCVC-SURF). I had just completed my junior year at Brown University, where I was studying Applied Mathematics-Biology (a joint degree offered by my college’s Applied Math department that focusses on using mathematical modeling and statistical analysis in biology). I knew I wanted to pursue my interests in mathematics and biology post-graduation but wasn’t sure how exactly they could be used together in a future career. Also, unlike some of my peers, I had no wet lab experience outside the classroom and was intimidated to commit myself to graduate studies and biology research without first understanding what it would be like. ter understand what kind of postgraduate study I would be The FCVC-SURF program was the perfect summer experi-

most passionate to pursue, and how I could apply my knowl-

ence: it exposed me to cutting-edge research in biology, but

edge to answer pertinent questions that could have a large

more than that, it gave me the opportunity to meet and learn

impact in medicine and society. In fact, without the FCVC-

from a wide range of doctors, scientists, and physician-sci-

SURF program, I would not have learned about or applied

entists who were free to pursue their passions for science in

to the graduate program in which I’m currently enrolled. It

ways that made a tangible difference in others’ lives. I worked

was at one of the SURF program’s talks that I heard from Dr.

for the lab of Dr. Jordan Shavit, a hematologist/oncologist

Santiago Schnell, who spoke about his journey to Michigan’s

who studies the genetics of blood clotting and its associated

MIP department and his experiences as a graduate mathe-

disorders in zebrafish. I assisted in the design and implemen-

matics student at the University of Oxford. From him, I came

tation of a mutagenesis screen for modifiers of thrombosis. I

to learn about the mathematicians in Oxford’s Mathematical

learned how to perform a variety of techniques that I had only

Biology group, who were using the same modeling and sta-

heard about in my courses, in addition to some that I hadn’t

tistical techniques from my undergraduate courses to assist

even imagined existed. I gained a better appreciation for the

experimentalists and doctors in research and in the clinic. Dr.

nature of research and came to love it by the end of my time

Schnell’s enthusiasm for his graduate education, his mentors,

at Michigan. I quickly became close friends with other mem-

and his current research inspired me to apply to the Univer-

bers of my cohort, and together we enjoyed the sights and

sity of Oxford, where I am currently in my second year as a

wonderful aspects Ann Arbor had to offer. I still have a small

DPhil student, developing and analyzing mathematical mod-

photo that I found at the city’s annual art fair decorating my

els for angiogenesis and neural crest cell migration.

room back home.

Thanks to the FCVC-SURF program, I gained confidence in

The most special aspect of the FCVC-SURF program was the

my ability to pursue biomedical research and discovered the

weekly talks I attended as part of the program, in which fac-

perfect graduate program for my background and research

ulty members from the FCVC and MIP came to discuss their

interests. I would like to thank all those involved with the MIP

career paths, the story behind their research interests, and

summer programs for providing the opportunity to take my

their advice for undergraduates like myself (these were joint

first genuine step into science, for giving undergraduate stu-

talks among the FCVC-SURF and other MIP summer under-

dents like me a chance to experience what research and life

graduate research programs). By hearing about these re-

as a graduate student is like, and for helping me learn about

searchers’ pathways into biomedical research, I came to bet-

what careers exist in medicine and biology post-graduation.

20

Physiology Matters

The Early Years of Physiology at Michigan A highlight of the early history of our department from the University of Michigan Encyclopedic Survey, Bicentennial Edition.

T

he Department of Physiology at the University of

laboratories.

The research mission was also strong and

Michigan was one of the first basic science departments

innovative, facilitated by an experienced Instrument and

at a Medical School in the United States. Now renamed

Electronics Shop, which made custom-designed equipment

Department of Molecular & Integrative Physiology, the

for experiments and student laboratories.

department has continually been noted for its strong emphasis

leadership of early Department Chairs, H. Sewall (1882), W.H.

Under the

on education at all levels, for its landmark research and for its

Howell (1889), W.P. Lombard (1892), and R. Gesell (1923),

contributions to leadership in the scientific community.

research programs focused on respiratory physiology and neurophysiology, and the Department had strong links with

Below we share a brief highlight of the early history of our

Physics and Engineering. Gesell was dedicated to the humane

department prepared by Dr. Jessica Schwartz with Drs. Fred

treatment of animals, which led to the establishment of the

Karsch, John McReynolds, John Williams for the University

Unit for Laboratory Animal Medicine, directed for many years

of Michigan Bicentennial (2017). The most recent edition of

by Physiology Professor Bennett Cohen.

our department history is available through the University of Michigan: An Encyclopedic Survey – Bicentennial Education

The Physiology Department at Michigan remained at the

on https://www.lib.umich.edu/database/link/44263

forefront of the field, participating actively in the founding of the American Physiological Society in 1887; four of the

Essential roles of Physiology in the early years of the

28 charter members were associated with the University of

Medical School:

Michigan. Another notable early contribution of the Michigan

Physiology has been an essential part of the University

Physiology Department to the field was A Brief Text of

of Michigan Medical School curriculum since the Medical

Physiology for Dental, Premedical and College Students by Carl

School was founded. Initially, Physiology was taught in

Wiggers, a medical student and subsequently an Instructor

the Departments of Medicine and Surgery, but it was

in Physiology, who went on to become an internationally-

so

Physiology

recognized cardiovascular physiologist. Both leadership and

Department was established as one of the earliest in the US.

the writing of definitive textbooks were to become continuing

Dedicated to its teaching mission, the early Department of

traditions of the faculty of the Physiology Department at

Physiology devoted an entire floor of East Medical Building

Michigan, helping mainting the prominence of the Department

(now the 1100 North University Avenue Building) to student

to the present day.

fundamental

that

in

1882

a

separate

Physiology Matters

21

scholarly scientific impact. But I am most impressed by our PhD students’ success over the last couple of years in writing and being awarded Individual Pre-doctoral Fellowships.

These fellowships from the National Institutes of Health, the American Heart Association, the Howard Hughes Medical Institute, National Science Foundation, and other groups are nationally competitive (extremely competitive) and provide funding for the student’s research stipend and benefits. The student’s proposals are typically judged on three main criteria: 1) the accomplishments of the student 2) the training environment and 3) the scientific impact of the research proposal. While the awarding of these fellowships recognizes our amazing students and the strong training environment within our mentor laboratories and the graduate program in Physiology, in the end, the most important factor in the score is the OVERALL SCIENTIFIC IMPACT of the proposed research. Our students are tackling fascinating scientific questions, uncovering mechanisms of human disease, and designing and testing new possible therapies that one day may make an impact on the treatment of patients, and these awarded fellowships

Scientific Impact

By Daniel Michele Graduate Chair & Professor, Molecular & Integrative Physiology

prove it.

But SCIENTIFIC IMPACT does not begin and end in the research laboratory. Our students continue to amaze me with their after-hours and tireless efforts toward improving our scientific community and reaching out to young students for whom science is not visible or a part of their career aspirations.

Many of our students serve as mentors for the

University of Michigan Undergraduate Research Opportunity

S

CIENTIFIC IMPACT. It is a term that all scientists know

Program and our department's summer fellowship program

very well. All major funding agencies that award re-

students who are seeking their very first research experienc-

search grants have at least one major scoring criteria

es. Several of our students also volunteer and serve in lead-

related to scientific impact. In fact, for the National Institutes

ership positions in student organizations that seek to support

of Health, after the entire review of a grant proposal is com-

current graduate students, including students from under-

pleted, the reviewer is asked to give a final score based on

represented backgrounds and students with disabilities. Our

the “Overall Scientific Impact”. This one impact score, which

Science Engagement and Education for Kids program, found-

in the end is what basically determines if the grant is funded,

ed and run entirely by students, continues to reach out to

boils down the entire evaluation to “How will this proposed

underserved elementary schools in Ypsilanti and Southeast

research impact our new knowledge of how biology/physiol-

Michigan to provide science education opportunities where no

ogy works? and/or “How will this proposed research impact

science curriculum currently exists.

our understanding and treatment of significant human dis-

efforts, the future of science is bright as our students are not

eases?” If the “Overall Scientific Impact” is considered “Out-

only becoming outstanding scientists, but are engaged and

standing”, the grant proposal will very likely be funded, de-

committed to making science accessible, more diverse, and

spite the current low success rates of major grant proposals.

more visible to the broader public and beyond.

As I look over the past year, the graduate students in the

All of these accomplishments of our students give great

Molecuar & Integrative Physiology PhD graduate program

“bragging rights” and news material for our graduate program

are having outstanding SCIENTIFIC IMPACT.

Our students

director’s and our department’s Twitter accounts. If you want

have published several outstanding first author papers in

to keep up with our student’s accomplishments in real-time, I

major scientific journals.

I could also tout the many suc-

encourage you to follow us at @UMPhysiology. Find out more

cessful dissertation defenses, where the dissertation commit-

about the SCIENTIFIC IMPACT of our students and I am sure

tees award degrees based on the main criteria of significant

you will agree…it is “Outstanding!”

22

Physiology Matters

With their outstanding

CONGRATULATIONS 2019 PhD Graduates

HAOCHENG LU

JEANINE RUGGERI

ANDREW SCHWARTZ

Eugene Chen Lab

Howard Crawford Lab

Yatrik Shah Lab

“The Role of Transcription Factor EB in the Vascular Wall Biology”

“Determining the Role of Discoidin Domain Receptors in the Pathogenesis of Pancreatic Ductal Adenocarcinoma”

“Hepcidin/Ferroportin/HIF-2 Regulation of Iron Metabolism at the Systemic and Cellular Level “

SUROJIT SURAL

KEVIN SWIFT

Allen Hsu/Scott Pletcher Labs

Gina Poe Lab

“Roles of HSB-1 in Regulation of Heat Shock Factor Activity, Histone Levels, Mitochondrial Function and Longevity”

“Locus Coeruleus Optogenetic timulation and the Estrous Cycle Manipulate Sleep Character stics and Memory Consolidation”

Physiology Matters

23

Frosty Reception

by James Dau (Reprinted from Discover Rackham: https://rackham.umich.edu/discover-rackham/frostyreception)

“Sensory biology is fascinating because we have all these sensory cues that shape our reality,” Ronan says. Going deep to our most basic mechanisms is very satisfying.”

There’s no mistaking when it’s cold outside, but how our bodies know that has been an open question. Molecular & Integrative Physiology Ph.D. student Elizabeth Ronan is working to understand where that chilly feeling comes from.

T

he ability to sense temperature is essential for the sur-

opposite end of the thermometer. While past research has

vival of humans and most other organisms. Being able

identified one cold receptor—called TRPM8—it only activates

to feel when, and in which direction, the temperature

at around 26 degrees Celsius (about 79 degrees Fahrenheit),

is changing tells us when to seek shelter, bundle up, or pay

and anyone who’s endured a mid-December polar vortex

more attention to how much water we’re drinking. Under-

knows the body is capable of feeling much colder tempera-

standing how our bodies convey this critical information about

tures. Thanks to a new approach and the creative adaptation

our surroundings has been the subject of considerable re-

of existing lab technologies, however, Department of Molec-

search over the years, with important implications for medical

ular & Integrative Physiology Ph.D. student Elizabeth Ronan

therapies and pain management.

and her colleagues in the lab of Shawn Xu, the Bernard W. Agranoff Collegiate Professor in the Life Sciences, have finally

These efforts have yielded significant progress in understand-

begun chipping away at this long-frozen question.

ing how the body senses heat. Scientists have been able to produce experiments that pinpointed the body’s heat recep-

“Cold sensitivity has been a long-term project in our lab,”

tors, as well as how they function. Administering cold with

Ronan says. “Past research has shown receptors for cool tem-

similar precision has proven much more challenging, howev-

peratures, but this research is the first time a sensor for nox-

er, and as a result there has been much less progress on the

ious, painful cold has been found to exist in nature.”

24

Physiology Matters

An Elegans Solution

advantage of its easily manipulated genome, they then gen-

As is often the case, the key to deciphering the riddle of cold

erated 30,000 unique mutant strains of C. elegans. With one

sensation came from one of the most unassuming places, in

strain in each of the thermocycler’s 96 test tube wells, they

this case a diminutive roundworm named Caenorhabditis ele-

dropped the temperature and observed which worms re-

gans, commonly known as C. elegans. Widely used as a mod-

sponded to the newly frigid conditions and which did not. The

el organism in research, C. elegans possesses an easily ma-

researchers identified that those lacking cold responses pos-

nipulated genetic code, with at least 70 percent of its genes

sessed mutations in the gene encoding a glutamate receptor

highly conserved in higher-order species, including humans.

called GLR-3.

In addition, and with particular importance for Ronan and her fellow researchers, the worm is the only organism for which

In response to sudden drops in temperature, worms with nor-

scientists have a complete connectome—a comprehensive

mal GLR-3 functionality increased what Ronan calls avoidance

map of every connection between neurons in its body, akin to

behavior—the worms began to move backward and turn, look-

a wiring diagram for a living organism.

ing for an escape to more favorable conditions—while mutant strains that did not showed no change. Further experiments

“Sensory biology is fascinating because we have all these

conducted by Ronan confirmed that GLR-3 was required for

sensory cues that shape our reality,” Ronan says. “Going deep

the cold avoidance response.

to our most basic mechanisms is very satisfying.”

“We found that GLR-3 activated at 18 degrees Celsius, well “C. elegans is ideal for exploring basic, evolutionarily con-

below the threshold of the cool sensor TRPM8,” Ronan says.

served mechanisms,” Ronan explains. “Because its genome

“These experiments showed its importance for noxious cold

is relatively simple, it’s a lot easier to identify new genes that

sensing, now we had to see if it was filling the same role in

would be much harder to find in more complex species. Com-

other species and, ultimately, how it was doing so.”

bined with knowing how every one of its neurons are connected, it’s an ideal model for sensory biology.”

Mice, fish, and humans all possess a homolog—a gene related to another gene by common ancestry—to GLR-3, called

That still left the question of having the right technology, the

GluK2. In order to test whether GluK2 provides the same ser-

same issue that had plagued cold sensation researchers for

vice as its ancestral counterpart, Ronan and her colleagues

years. Fortunately, C. elegans provided an answer for that,

conducted heterologous experiments—in which scientists ex-

too.

press genes in cell lines—on all three homologs and confirmed that their expression does, in fact, confer cold sensitivity just

Previous work in the Xu lab identified that the intestine of

like GLR-3 in C. elegans. The team also confirmed that DRG

C. elegans is cold-sensitive, playing an important role in ex-

neurons—peripheral sensory neurons in mammals that detect

tending its lifespan under cold temperatures. The researchers

a variety of external stimuli—in mice also depend on GluK2

discovered that in cold environments, the genes mediating

for their response to cold.

longevity are activated, extending its lifespan at low temperatures. This discovery presented an ideal way to perform an

Ronan says additional research to determine how exactly

unbiased genetic screen for the elusive cold sensor.

GLR-3 and GluK2 sense cold is already under way. That research could eventually lead to better medical therapies, but

Many labs that host biological, genetic, or biomedical re-

it’s already yielded a more complete understanding of how

search employ devices called quantitative polymerase chain

the body functions.

reaction (qPCR) thermocyclers. Conventionally used to amplify and quantify DNA, qPCR thermocyclers are capable of

“We’re laying the foundation for understanding the mecha-

rapidly heating and cooling dozens of test tubes at once while

nisms that drive cold response that future research and future

measuring fluorescence intensity to quantify gene expression

scientists can use to directly benefit human health,” Ronan

level. And it didn’t escape the team’s notice that C. elegans

says. “We’ve provided a big missing piece in temperature sen-

were just about the right size to fit in a test tube.

sation, one that can help us understand how our own bodies survive and function.”

To identify new cold sensing genes, the team placed C. elegans specimens expressing GCaMP—a genetically encoded calcium indicator that increases in fluorescence when activated—in the intestine directly into the qPCR test tube wells, and observed that upon cooling in the thermocycler they could detect an increase in intestine fluorescent intensity. Taking

Physiology Matters

25

Physiology on the Cover Christin Carter-Su Lab

Malcolm Low Lab Daniela Orquera et al.

The homeodomain transcription factor NKX2.1 is essential for the early specification of melanocortin neuron identity and activates Pomc expression in the developing hypothalamus. Journal of Neuroscience 2019; 39: 4023-4035

Ormond MacDougald Lab Ziru Li et al. G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche. Journal of Clinical Investigation 2019;129:2404–2416

Suzanne Moenter Lab Caroline Adams et al.

Changes in both neuron intrinsic properties and neurotransmission are needed to drive the increase in GnRH neuron firing rate during estradiol positive feedback. Journal of Neuroscience 2019, 39: 2091-2101

Anabel Flores et al. Crucial Role of the SH2B1 PH Domain for the Control of Energy Balance. Diabetes 2019; 68: 2049-2062

Ling Qi Lab Yewei Ji et al. Toll-like receptors TLR2 and TLR4 block the replication of pancreatic β cells in diet-induced obesity. Nature Immunology 2019; 20: 677–686

26

Physiology Matters

Philanthropy Funds

W

e hope our successes this past year makes you proud of the University of Michigan Department of Molecular & Integrative Physiology. Our philanthropy funds play a key role in strengthening our department, faculty, and trainees. We hope you will play part and join many others in supporting Molecular & Integrative Physiolo-

gy by making a gift to the funds below.

Bishr Omary Physiology Postdoctoral Awards & Symposium Fund Your gift will be used to support Molecular & Integrative Physiology postdoctoral career development in a variety of ways that include postdoc recognitions, the annual symposium, a named lectureship in conjunction with the annual symposium, postdoc travel and small grants, and other postdoctoral career development activities.

Donate online at https://www.giving.umich.edu/give/335629 Graduate Education Fund in Physiology Your gift will propel the development of future biomedical researchers currently enrolled in the Molecular & Integrative Physiology PhD Program. These individuals are studying the mechanistic basis of human diseases such as cancer, diabetes, and obesity. Donate online at http://victors.us/mipgraduate John and Margaret Faulkner Lectureship You will be supporting an annual lectureship by a prominent invited speaker selected by the students and faculty in honor of John and Margaret Faulkner. Donate online at http://victors.us/faulknerfund Master’s Education Fund in Physiology The MS in Physiology is designed for students who plan to pursue employment in a research laboratory, or to continue their education as PhD, medical, dental or other health professional schools. Your gift will provide financial assistant to master students. Donate online at http://victors.us/mipmaster Physiology Annual Fund Your gift enables the Department of Molecular & Integrative Physiology to direct resources where they are most needed or where opportunities are greatest, from upgrading or replacing a critical piece of lab equipment to providing resources to our trainees, researchers and faculty. Donate online at http://victors.us/mipfund Physiology Summer Research Fellows Fund Your gift will support undergraduate students that are interested in research in physiology and/or biomedical sciences.

This fund provides financial support to summer research fellows, their research and the summer program activities.

Donate online at http://victors.us/mipsummer SEEK Fund The Science Engagement and Education for Kids (SEEK) is an outreach effort driven by the physiology students and department members to promote science in the community. This fund supports the development of outreach educational program and outreach activities. Donate online at http://victors.us/mipseek If you would like to discuss making a major donation to any of the above funds, leaving a gift for us in your will, or offering a pledge or gift of appreciated stock, please contact Chrissy Barua, our development officer, at 734-763-4938, or cebarua@umich.edu.

Physiology Matters

27

28

Physiology Matters