Biology Highlights 2021, Harvey Mudd College

B I OLOGY HIGHLIGHTS 2021

Update from the Department Chair Dear Alumni, Parents and Friends of HMC Biology, I’m happy to share the 2021 Biology Highlights newsletter with you. During this pandemic year, a continuous theme in our department has been making lemonade from lemons.

That spirit showed up strongly in the work of our seniors. Many of them had intended to do hands-on work, which was not possible in the pandemic. Despite that, they found creative ways to do a capstone—from connecting art and biology to building a speech-to-text lab notebook.

Faculty members have also managed to pull good things out of a challenging situation.

Those who do experimental work have found ways to keep their programs moving forward, despite the lack of in-person students. This year they published more than a dozen research papers, and received several grants, including an NSF CAREER award (to Danae Schulz). They’ve also continued to deliver the curriculum. This meant converting everything they do into an online format. Laboratory classes presented an especial challenge, but professors found ways to make the most of what was possible.

This year we mourned the passing of Bill

HARVEY MUDD COLLEGE | BIOLOGY HIGHLIGHTS 2021

Purves, the founding chair of the department.

He was a person who touched many lives while he was here, and he will be missed.

As I write this in the spring, it’s a time to look forward. This year, the graduation celebrations were virtual again, but there are plans to have an in-person commencement next year for the Class of 2020 and the Class of 2021. This year’s seniors are going out into a changed world. But, as usual, they have found great things to do with themselves ranging from graduate programs to positions in companies and labs.

I’m pleased to say that we will have on-campus student research this summer. And we’re looking forward (really, really looking forward) to having a full complement of students on campus in the fall. Next year it should also be possible to start having alumni events again. I look forward to seeing some of you on campus next spring!

Eliot C. Bush Chair, Department of Biology bush@hmc.edu

African Trypanosome Research Published Along with student researchers and faculty collaborators, biology professor Danae Schulz has published research in PLOS Neglected Tropical Diseases that investigates ways to inhibit the growth of the parasite, Trypanosoma brucei.

Schulz, Matty Walsh ’20, Ellie Naudzius ’20, Savanah Diaz ’22, Theodore Wismar ’22 and Keck Graduate Institute

associate professor Mikhail Martchenko Shilman are co-authors of “Identification of Clinically Approved Small Molecules That Inhibit Growth and Affect Transcript Levels of Developmentally Regulated Genes in the African Trypanosome.”

Trypanosoma brucei is a Sub-Saharan African protozoan parasite that, when transmitted to the bloodstream of a mammal through the bite of a tsetse fly, causes fatal disease in humans and animals. Existing drug therapies are difficult to administer and can have serious side effects, and resistance to some drugs is increasing, creating an urgent need for alternative trypanosomiasis therapeutics.

The PLOS paper is an extension of work Schulz published as a postdoc on bromodomain proteins. “In that work, we showed that small molecules that inhibited bromodomain proteins could push parasites that started out in the mammalian stage of the life cycle toward a form of the parasite usually found only in insects,” says Schulz. “This was therapeutically interesting, since parasites adapted for the insect stage would be expected to not survive well in a mammal. In other words, if a mammal infected with the parasites were treated with a drug that made the parasites adapted to be in the insect stage, the parasites would be maladapted for survival in the mammal, offering an opportunity for the immune system to clear the infection. That would be a big leap forward.”

More recently, Schulz and her undergraduate researchers have been trying to determine if there were other small molecules already on the market (clinically approved) that could do what the bromodomain inhibitor did, i.e., push the mammalian form of the parasite forward to the insect form.

Danae Schulz

Ocean Conditions Linked to Coral Evolution A study conducted by Harvey Mudd College biologists provides evidence that ocean geochemistry drives patterns of morphological evolution in anthozoans (corals and sea anemones).

Biology professor Catherine McFadden, Andrea Quattrini (former HMC postdoctoral researcher, now a research zoologist and curator of corals at the Smithsonian Institution) and Estefanía Rodríguez, a curator at the American Museum of Natural History, published the research in the journal Nature Ecology and Evolution. The scientists spent several years on the project, including time to develop a target-enrichment technique for genomic sequencing of anthozoan species.

“It took us about two years just to work out all of the kinks in the DNA sequencing protocol we developed,” says McFadden, Vivian and D. Kenneth Baker Professor of Life Sciences. “We didn’t get the sequence data that underlies this paper until early 2018, and the complicated

HARVEY MUDD COLLEGE | BIOLOGY HIGHLIGHTS 2021

and time-consuming bioinformatic analyses then took another two years.”

The researchers analyzed hundreds of anthozoan specimens from museum collections around the world, then aligned the molecular data with fossil evidence of anthozoan history. The result is a phylogeny showing that anthozoans have existed on Earth for 770 million years, long enough to experience massive shifts in climate, fluctuations in ocean chemistry and several mass extinctions.

It also provides a framework for predicting how well stony corals and soft corals will fare under impending global warming and ocean acidification.

In short, stony corals (the hard-bodied corals that build the foundations of coral reefs) will likely continue to diminish under changing environmental conditions. However, the evolutionary history of Anthozoa suggests other groups (soft corals, anemones) will persist and diversify in their wake.

Several students in McFadden’s lab contributed to this research and related projects, including Alicia Pentico ’19, Justin Jiang ’23 (as a high school student), Brooks Macdonald ’20, Johnson Hoang ’20, Natasha Floerke ’19, Katie Erickson ’19, Aaron Friend ’17 and Emily Petroni ’21.

A coral reef dominated by soft corals.

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In Memoriam: Biology Department Founder William K. Purves

William K. Purves, the founding member and former chair of the Department of Biology, passed away April 22 in Costa Mesa with family at his side.

Purves was the Stuart Mudd Professor of Biology from 1977 to 1995. He served as chair of the department of computer science from 1985 to 1990 and of the department of biology from 1985 to 1995.

He elected early retirement in 1995 after teaching introductory biology for 34 consecutive years in order to concentrate entirely on research directed at learning and scientific education. The move grew from his association with Roger Schank, first in his Artificial Intelligence Group at Yale, then in his Institute for the Learning Sciences at Northwestern University, and in his activities at Carnegie-Mellon University, Engines for Education, Socratic Arts, and Grandview School. Purves participated in the development of Schank’s Virtual International Science and Technology Academy.

Purves was the senior author of the first seven editions of the college textbook Life: The Science of Biology. The eighth edition was coauthored with David Sadava, Craig Heller, Gordon Orians and David M. Hillis.

A fellow of the American Association for the Advancement of Science, Purves served as head of the Life Sciences Group at the University of Connecticut, Storrs, and as chair of the Department of Biological Sciences, University of California, Santa Barbara, where he won the Harold J. Plous Award for teaching excellence.

HARVEY MUDD COLLEGE | BIOLOGY HIGHLIGHTS 2021

Purves was a co-founder and scientific director of The Mona Group LLC, which combined the diverse talents of its partners (pedagogy and scientific content, programming, art, animation and publishing) to design, develop, produce, manufacture and market interactive multimedia educational software products. He consulted on education and training for Motorola, Edvotek and other companies.

Purves attended the California Institute of Technology, obtaining a bachelor of science degree in 1956. He continued his studies at Yale University, completing a master of science in 1957 and a doctor of philosophy in 1959 under Arthur Galston. He was a postdoctoral fellow (1959–1960) with the National Science Foundation at the University of Tübingen, and was a postdoctoral fellow (1960–1961) with the National Cancer Institute at the University of California, Los Angeles. Purves served in a senior postdoctoral fellowship with the National Science Foundation at the University of London in 1967.

Purves is the 1994 recipient of a Harvey Mudd Honorary Alumni Award and the 1995 Henry T. Mudd Prize, which recognizes outstanding members of the HMC community.

He is survived by his wife, Jean; son, David; and grandchild, James. The family requests that gifts in his honor be made to the William Purves Endowed Life Science Summer Research Fund at HMC or to Parkinson’s disease research.

Bill Purves and Anne Marie Stomp, then a PhD candidate from the University of Connecticut, set up and taught the first HMC biology laboratory.

“In the Beginning, There Was Bill” On the occasion of the 35th anniversary of the Department of Biology, the College featured an interview with Bill Purves in the spring 2013 HMC Bulletin.

Read the interview.

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Promotions Biology faculty receive promotion or tenure appointments, effective July 1, 2020 Karl Haushalter received promotion to full professor. Hired in 2003, he researches DNA

repair processes to understand the molecular mechanisms of carcinogenesis, aging and evolution. Haushalter is active in community efforts to combat the stigma associated with HIV-AIDS and support those living with HIV-AIDS through education and empowerment.

The HIV-AIDS: Science, Society and Service class that he teaches is an integrative experience, service-learning course that addresses both the science of HIV and the ways that the HIV epidemic has impacted communities.

Matina Donaldson-Matasci and Jae Hur received tenure and promotion to the rank of associate professor. Donaldson-Matasci studies how colonies of social insects, such as bees and ants, coordinate group behaviors. Hur studies the fundamental genetic and physiological pathways that govern organismal lifespan.

Danae Schulz was appointed for a second, two-year term as assistant professor.

Schulz studies the African trypanosome, a protozoan parasite that causes sleeping sickness in humans and nagana in cattle.

Postdoctoral Program Scholars In 2020, the College introduced the Postdoctoral Program in Interdisciplinary Computation (PIC), a pilot three-year program that responds to the increased demand for faculty members equipped with the ability to teach computational skills within a wide variety of disciplines. As part of the program, PIC scholars collaborate with HMC faculty members to conduct research. Two of the scholars have been teamed with biology faculty members.

Joseph Wirth is

researching microbial genome evolution with Eliot Bush, professor of biology and department chair. Wirth earned his PhD in microbiology from Franklin College of Liberal Arts and Sciences, University of Georgia, and was a postdoctoral research associate in the lab of Robert J. Maier. An expert in the microbial physiology of pathogenic bacteria, he is investigating the roles of putative genes involved in virulence and oxidative stress in Campylobacter concisus, Campylobacter jejuni and Helicobacter hepaticus using molecular genetics and biochemical technique.

Morgan CarrMarkell is studying

Karl Haushalter

Matina Donaldson-Matasci

Jae Hur

Danae Schulz

HARVEY MUDD COLLEGE | BIOLOGY HIGHLIGHTS 2021

collective behavior in social insects with Matina DonaldsonMatasci, Barbara Stokes Dewey Assistant Professor of Biology. CarrMarkell is a PhD candidate at the University of Minnesota, studying honeybee foraging behavior in landscapes with reconstructed prairie ecosystems. She began studying honeybees as an undergraduate at Wellesley College and continued studying them for her master’s degree at the University of Illinois at Urbana-Champaign, where she started keeping her own colonies as a hobby. She enjoys learning and teaching about biological systems, especially how interacting individuals can make collective decisions without any central authority telling them what to do.

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Guerra Earns Master’s and Promotes Leadership and Social Justice at HMC

Fiona Tay ’12 and Elaine Guerra

Elaine Guerra, biology department lab manager at Harvey Mudd College, earned a master’s of professional studies in psychology of leadership from Penn State World Campus in May. She’s now using her enhanced skills to foster effective leadership within the HMC community.

“I took one class per semester plus one accelerated course during the summers,” says Guerra, who continued to work full-time while in the online program. “I was in school continuously for about three-and-a-half years.”

Guerra says most of her courses focused on developing and understanding the person in a leadership role. Her favorite course, Dysfunctional Leadership, was a study of the ways an effective or developing leader could become derailed and make poor decisions that could negatively affect their followers and their organization. “What was compelling to me was the notion that derailment could happen

HARVEY MUDD COLLEGE | BIOLOGY HIGHLIGHTS 2021

to anyone,” she says. “As leadership students, it was important for us to understand toxicleader behavior and avoid it so we could make good, ethical decisions.”

Among the insights Guerra gained through the program was an understanding of how the concept of leadership encompasses not just the individual leader, but also the people being led and the interactions between them in various situations. “Effective leadership cannot be built without fostering trust in your followers,” Guerra says. “What builds trust is a concept called psychological safety.

This occurs when a leader promotes his or her organization’s culture that encourages risktaking in their followers. Without the fear of judgment or retribution, the followers will feel safe to counter or question the leader’s ideas or opinions. This kind of group dynamic will create more productive outcomes and foster innovation.”

At Harvey Mudd, Guerra is participating in the Intergroup Dialogue Program through the Office of Institutional Diversity. “Since many of the papers I wrote for my master’s were based on social justice, a subject I am passionate

about, I decided to become a social justice facilitator at HMC,” she says. In spring, Guerra and other facilitators will begin moderating weekly small-group discussions with students about topics like race, ableism, religion, ethnicity, social class, sexual orientation, gender and more. The dialogues are designed to help participants create spaces for learning and engagement across differences. Specific to Guerra’s expertise, the discussions are an opportunity to use her skills in facilitating and leading diverse groups within classrooms, organizations and communities. “Many of the skills I learned in leading small groups will come in handy when I get a chance to facilitate the students’ learning as we strive toward a socially just environment,” she says.

In addition to putting her leadership skills into practice around social justice issues, Guerra hopes to inspire other people to pursue their goals. “I received my master’s in May 2020, when I was 60 years old,” she says. “I want to serve as a role model for anyone who is thinking of going back to school but is afraid it is too late. I say it is never too late to learn something new!”

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Biology Talks In March 2020, shortly after the College transitioned to online instruction, the HMC community began mobilizing to help address urgent local, national and international needs arising from the COVID-19 crisis. In the College’s first Mudd Talks series event in April 2020, Nadia Abuelezam ’09 (mathematical biology), epidemiologist and assistant professor at the Boston College William F. Connell School of Nursing, spoke via Zoom with Karl Haushalter, associate professor of chemistry and biology. The two discussed the coronavirus pandemic and the latest research and information regarding the novel coronavirus.

In May 2020, Eliot Bush shared a presentation on how scientists determine the evolution of viruses, specifically the novel coronavirus, SARS-CoV-2, and how we can know that the virus originated in bats. Video of both presentations are available for streaming on the College’s YouTube channel.

In July 2020, computer science professor YiChieh (Jessica) Wu facilitated a Zoom series of talks related to computational biology. Here are abstracts from the speakers’ presentations:

“Modeling the Evolution of Cell Types in the Central Nervous System” Andreas Pfenning, assistant professor, Computational Biology Department, School of Computer Science, Carnegie Mellon University The brain is an enormously complex organ— even a tiny piece of human brain tissue can contain dozens of different subtypes of neurons, each of which play distinct roles in the neural circuits underlying complex behaviors. New technologies for measuring levels of genes within single cells have provided us with a molecular atlas of these cell types in several mammalian species, but the rapid pace of evolution has made it difficult to reliably trace some neural cell populations across many species over large evolutionary distances. Here, we develop a new computational approach, TMNT (toolkit for modeling nested trees), that jointly models the hierarchy of cell types, species and brain regions to identify new evolutionary events. When applied to study retinal cell types, our tool identifies new patterns of gene expression and subtypes of rod cells that emerge in species with night vision.

HARVEY MUDD COLLEGE | BIOLOGY HIGHLIGHTS 2021

“Generating Interpretable Visualizations of Single Cell Genomic Data” Gerald Quon, assistant professor, Department of Molecular and Cellular Biology, UC Davis; member of the Genome Center and UC Davis Comprehensive Cancer Center Non-linear dimensionality reduction methods such as t-SNE and UMAP are standard tools for visualizing and exploring genomic datasets.

Their principal limitation is that they are not interpretable; it is incredibly challenging to infer how variation along different axes of their plots is related to variation in the original features, such as gene expression patterns. In this talk, I will discuss the development of a scalable, interpretable variational autoencoder (siVAE), a non-linear dimensionality reduction method that can generate embeddings qualitatively similar to t-SNE and UMAP but are interpretable by default. That is, siVAE infers a loading matrix during training that maps contributions of input features (genes) to each axis of the visualization. I will illustrate how siVAE enables fast identification of genes that principally distinguish different cell types and states on different genomic data.

Inference of Regulatory Network Dynamics on Developmental Lineages Sushmita Roy, associate professor, Biostatistics and Medical Informatics Department; faculty member, Wisconsin Institute for Discovery, University of Wisconsin, Madison Regulatory networks connect regulatory proteins (e.g., transcription factors and signaling proteins) to target genes and control what genes are expressed when translating the information encoded in an organism’s genome to context-specific responses. Identification of these networks is important to advance our understanding of many biological processes such as development, disease, response to stress and evolution. In this talk, I will present computational methods to tackle a few key problems in understanding network dynamics on developmental lineages. Using these approaches, we have derived useful insights about mammalian gene regulation including the identification of key regulators in host response and chromatin state dynamics during cell state transitions.

Deep Learning the Regulatory Code of the Human Genome Anshul Kundaje, assistant professor of genetics and computer science, Stanford University The human genome contains the fundamental code that defines the identity and function of all the cell types and tissues in the human body. Genes are functional sequence units that encode for proteins. But they account for just about 2% of the three billion long human genome sequence. What does the rest of the genome encode? How is gene activity controlled in each cell type? Where do the regulatory control elements lie and what is their sequence composition? How do variants and mutations in the genome sequence affect cellular function and disease?

These are fundamental questions that remain largely unanswered. The regulatory code that controls gene activity consists of DNA words with complex syntax and grammar (akin to natural language) encoded within hierarchically organized units of regulatory elements. These syntactic units of functional DNA words are sparsely distributed across billions of nucleotides of genomic sequence and remain largely elusive. Deep learning has revolutionized our understanding of natural language, speech and vision. We strongly believe it has the potential to revolutionize our understanding of the regulatory language of the genome. We have developed integrative supervised deep learning frameworks to learn how genomic sequence encodes millions of experimentally measured regulatory genomic events across hundreds of cell types and tissues. We have developed novel methods to interpret our models and extract local and global predictive patterns revealing many insights into the regulatory code. We will demonstrate how we can use deep learning models as oracles and perform millions of in-silico experiments to reveal the regulatory code. Our models also allow us to predict the effects of natural and disease-associated genetic variation i.e. how differences in DNA sequence across healthy and diseased individuals are likely to affect molecular mechanisms associated with complex traits and diseases.

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2019–2020 Biology Department Awards W.A. Brandenburger Biology Prize

Biology Writing Fellows

Awarded annually to a senior biology major for outstanding performance and promise in the field of biology.

The department annually appoints students who have demonstrated great prowess in the field of scientific writing.

Ivy Liu ’20

Emily Shimizu ’20, Matty Walsh ’20

William K. Purves Biology Prize

Best Senior Thesis

Awarded to a junior biology major who combines scholarship with some kind of breadth (intellectual, cultural, athletic or service).

Awarded annually to a senior or seniors with an outstanding research project during their capstone.

Sarah Halvorsen ’20, Gabby Teodoro ’20

Matty Walsh ’20, Arya Massarat ’20

2019–2020 Thesis Projects Johnson Hoang ’20: RpoS, an E. coli Sigma Factor, is Responsible for the General Stress Response in the Bacterium

Elena V. Romero ’20: How Do C. varians Colonies Coordinate the Allocation of Workers Among Nests?

Advisor: Daniel Stoebel, associate professor of biology

Advisor: Matina Donaldson-Matasci, assistant professor of biology

Arya Massarat ’20: Mapping Floral Resources for Bees Using

Matty Walsh ’20: Genetic Screen for Genes That Induce

Drone Imagery

Differentiation in Trypanosoma brucei

Advisor: Matina Donaldson-Matasci, assistant professor of biology

Advisor: Danae Schulz, assistant professor of biology

Lindsey Rollosson ’20: Localization of Bromodomain Proteins During T. Brucei Differentiation Advisor: Danae Schulz, assistant professor of biology

HARVEY MUDD COLLEGE | BIOLOGY HIGHLIGHTS 2021

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Alumni News

Peter Jarrell ’94: Kat and I have been enjoying Oregon for several years with our son, who recently turned 6. I’ve been with Genentech for 15 years. It was a great pleasure to come back to campus at the last *in person* Alumni Weekend and see how the bio department has progressed.

Yvonne Ulrich-Lai ’94: I am an associate

professor of pharmacology and systems biology at the University of Cincinnati School of Medicine. The goal of my research program is to identify the neural and hormonal substrates that are responsible for the interactions among diet, obesity and stress. This includes investigating how eating so-called “comfort” foods provides stress relief.

specialist, I mostly perform data abstraction for City of Hope’s cancer registries. On the side hustle front, I launched my one-woman ceramics business, Knick Natts, in 2015 and have enjoyed making and selling pottery at the semi-annual Brewery Artwalk in downtown Los Angeles. I fill my remaining free time with rock-climbing and crocheting—oh, and I was a (less-than-successful) contestant on Jeopardy! on Oct. 13, 2020, so I got to meet Alex Trebek.

Holly Johnsen ’07: I’ve been a data scientist

at Facebook in the Small Business Group for two years. Between Mudd and now, I spent two years teaching English in Japan, did a PhD in biology and taught elementary school math and science for two years. I’m married to a Mudder (we met in grad school), and we have a toddler.

Noah Levin ’02: I’ve been teaching philosophy at Golden West College (a California community college) for 10 years and live in Cypress, California, with my wife, Jenny, and our three children, Talia, Ronen and Ziva, who are all in elementary school.

HARVEY MUDD COLLEGE | BIOLOGY HIGHLIGHTS 2021

PhD student at the Albert Einstein College of Medicine, currently planning to defend my PhD thesis in summer 2021. Under the mentorship of Dr. Julie Secombe, I investigate the KDM5 family of chromatin modifiers, mutations of which are associated with heritable forms of intellectual disability. My thesis work aims to understand how KDM5 family proteins regulate neurodevelopment and cognitive function using Drosophila as a model organism. I am also an active member of the undergraduate education subcommittee at the American Academy of Neurology where I help develop policies and activities related to medical student neurology education. After graduation, I plan to pursue a residency in neurology and translational neuroscience research.

Simeon Koh ’12: I am a physician finishing up my third year of residency in internal medicine at Harbor-UCLA Medical Center. Afterward, I hope to do a one-year fellowship in palliative care and hospice medicine.

Trish Brock ’03:

I’ve been working at California State Polytechnic University, San Luis Obispo, for about 15 years, first helping submit grant applications, and more recently as director for research compliance. So now I review human subject and animal subject protocols and help faculty working on export-controlled projects and activities. It has been wonderful getting to use my broad Mudd education across a wide variety of projects and activities. I love living and working in the Central Coast and seeing lots of animals and life in my yard.

Hayden A. M. Hatch ’12: I am a sixth year MD/

Jessica Kurata ’12: I am working as a senior bioinformatic scientist at Guardant Health where we are working to develop a blood test to detect if a patient’s cancer has been completely removed by surgery or if they should still receive therapy.

Devon Stork ’15: I’ve been in a biochemistry Natt Supab ’08: After a long, meandering path trying jobs in several vastly different fields, including a year-long stint as a divemaster in Thailand, I finally returned to my scientific roots, so to speak. I’ve been working at City of Hope, a comprehensive cancer research hospital, for going on six years. In my current role as a disease registry systems

PhD program since my graduation, and this September I defended it. Now I’m planning to jump into the Boston biotech startup scene as soon as I can wrap up some publications.

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Alumni News Samuel Woodman ’16: This past summer,

Camille Goldman ’19: I am pursuing a PhD

I started work as a biologist/data manager for the Antarctic Ecosystems Research Group (AERD) at the National Oceanic and Atmospheric Association Southwest Fisheries Science Center. For the data manager side, I am coming up to speed on the databases used within AERD, as well as helping clean the data and develop tools to make it easily accessible to folks within the division. I am also working to establish a cloud storage system and data processing pipelines for our larger data, such as oceanographic data from underwater gliders and moorings and imagery and video data from cameras deployed on the gliders or penguins.

On the biologist side, I will be going to the field most years to help collect data on Antarctic penguins and pinnipeds.

in biomedical science at the Icahn School of Medicine at Mount Sinai. I have joined a lab that uses organoids (3D cell models) to study Parkinson’s disease. We are particularly interested in using our model to study geneenvironment interactions as most cases of PD have environmental causes that are not fully understood. Before COVID-19, I was taking full advantage of living in New York City. Now that I’m more confined to my tiny apartment, I spend my free time reading and baking. And yes, I do have a sourdough starter!

Your News Have you changed jobs? Retired?

Celebrated a milestone?

In addition to updates you submit, we compile information from a variety of sources: campus event notices, newspaper and magazine articles, press releases and Google alerts. Please submit updates to alumni@hmc.edu.

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