NYSCF News Update | Volume 14, Issue 1 by The New York Stem Cell Foundation

NYSCF

NEWSupdate VOLUME 14 ISSUE 1: 2021

The New York Stem Cell Foundation Research Institute

Uncovering the Secrets of Disease with Artificial Intelligence Diseases affect people differently, and drugs affect people differently. This is why we need precision medicine: the ability to deliver treatments that address each patient’s unique disease experience. But how do we tease apart what makes each patient distinct and create better therapies? One answer lies with artificial intelligence (AI). AI enables scientists to uncover hidden features of diseases, improve the way disease research is conducted, and develop personalized treatment plans.

Fibroblasts (cells that provide a structural framework for our tissues) stained to highlight different structures, made at the NYSCF Research Institute*

Identifying New Features of Disease Parkinson’s disease (PD) drugs have not fared well in clinical trials, suggesting that there is more to the disease than we currently understand. NYSCF scientists are using advanced imaging combined with AI analysis to unlock insights into what might drive the disease. “At NYSCF, we are using AI to study images of cells from PD patients at a whole new level, and have identified disease features invisible to the human eye,” said Bianca Migliori, PhD, NYSCF Senior Staff Data Scientist. “This work holds promise to accelerate drug development and precision medicine for this devastating disease.”

“At NYSCF, we are using AI to study images of cells from Parkinson's Disease patients at a whole new level, and have identified disease features invisible to the human eye.”

Accelerating Stem Cell Research AI is also improving how NYSCF scientists make stem cells. Without it, scientists have to manually examine dishes of cells to make sure they are developing properly. Now, thanks to a partnership with the Two Sigma Data Clinic – the pro bono data science and tech- for-good arm of Two Sigma – as well as a new AIdriven platform called Monoqlo developed by NYSCF scientists, robots can chip in to analyze images of growing cells and determine if they are ready to move on to the next stage of the process. This restores some of researchers’ most valuable asset: their time.

“Contributing to the NYSCF Global Stem Cell Array was a perfect project for Two Sigma’s Data Clinic as it combined both data science and programming, and it held promise to speed our understanding of disease and ultimately its treatment,” said Alfred Spector, Two Sigma’s CTO when the project began and now a Senior Scientific Advisor at NYSCF.

Tackling Mental Health Diagnosis NYSCF Innovators are also using AI to augment their research in novel and transformative ways. With his AI-driven platform Storyline, NYSCF – Robertson Neuroscience Investigator Alumnus Chris Gregg, PhD (University of Utah), aims to revolutionize the way we study and treat mental health disorders. Storyline participants record video responses to questions typically asked in a doctor’s office (i.e. “What is your biggest concern today?”) and submit them to a smartphone app. “We can analyze over 20,000 different features such as blood flow patterns, facial microexpressions, and word choice,” explained Dr. Gregg. “We hope to then use that information to determine the best care pathway for each person.”

Dopaminergic neurons derived from a Parkinson's disease patient at the NYSCF Research Institute*

All of this is just the beginning for AI in disease research, and we look forward to building on these exciting projects to accelerate personalized treatments for patients everywhere.

In this issue Meet Kay Unger Kay shares her vision for STEM page 3

2021 NYSCF – Druckenmiller Fellows Understanding eye disease, bone disease, and wound healing page 5

Can COVID-19 Cause Diabetes? New research suggests yes page 6

Inside the Aging Brain A window into Alzheimer’s page 7

WWW.NYSCF.ORG

Uniting to Accelerate Cures BOARD OF DIRECTORS Roy Geronemus, MD, Chairman Susan L. Solomon, CEO Margo Alexander Marilyn G. Breslow Peggy Brim Karen E. Burke, MD, PhD Francesco Clark Paul Goldberger George Lazarus, MD Richard J. Massey, PhD Paul M. Meister Siddhartha Mukherjee, MD, DPhil Stephen M. Ross Derrick Rossi, PhD Stephen M. Scherr Kay Unger Clyde Williams

LEADERSHIP COUNCIL Katherine Bristor & William Priest David A. Carmel Russell L. Carson Chuck Close* Alan M. Cohen Shirley Cook Fiona Druckenmiller Jodie & John Eastman Frank Gehry Lawrence E. Golub & Karen Finerman April Gornik Marlene Hess Tania Higgins Dorothy Lichtenstein Sandra Lloyd Stephen Meringoff David Mitnick Nancy & Fred Poses Carol Roaman Julian Robertson Clifford Ross Kara Ross Andy Russell Susan & Stephen Scherr Ian Schrager Barbara Stovall Smith Martha Stewart David & Jane* Walentas John Whitehead* Dick Wolf *In Memoriam

hese are unusual times for medical science: we are in an age of triumphant scientific accomplishments, with so much to celebrate, and yet we see more skepticism than ever before from a segment of the public that challenges the value of medical research and, indeed, even questions the very idea of scientific inquiry. NYSCF was founded with the goal of accelerating cures through the power of stem cell research, and a key part of our mission is to make an effort to enlighten the public about science and its potential for improving human life. We are scientists first and foremost, and NYSCF’s first obligation is to support the most advanced science there is—which also means to do all we can to encourage a climate that respects science and helps all to understand its benefits. We have so much good news to report. Thanks to the efforts of countless dedicated individuals, including our Board Member and NYSCF – Robertson Stem Cell Investigator Alumnus Derrick Rossi, PhD, a founder of Moderna Therapeutics, vaccines are reaching people around the globe. While there is still a long way to go before we emerge from the COVID-19 pandemic, I am heartened by the progress and by the role that our NYSCF community is playing in addressing so many aspects of the pandemic, including testing, drug discovery, and equity. I am also pleased to share updates on the exciting progress of our cell therapy for age-related macular degeneration (AMD). We are partnering with top surgeons at New York – Presbyterian Columbia University Irving Medical Center to restore sight for patients with AMD by replacing the eye cells they have lost with their own healthy eye cells, which we will make at NYSCF. Our facility for creating clinical-grade cells is now up and running, and NYSCF is on track to serve patients over the next year. This physician-sponsored clinical trial will yield one of the first stem-cell-based therapies in the world, and we are eager to bring this advancement to patients as quickly as possible. Over the past year, our daily lives have been touched by the urgency and importance of science, and of working together toward a brighter future. I am proud of everything that the incredible NYSCF community has accomplished together. With your ongoing support and partnership, we will continue accelerating the most promising science to help improve the lives of patients and their loved ones. I truly believe that despite the skepticism that often surrounds us, the future is bright. NYSCF is helping to make it so.

Susan L. Solomon, JD CEO and Founder

NYSCF CONFERENCE Keynote VIRTUAL CON FEREN CE

ONYSCFNEWS C TO B E Rupdate 19-20, 2021

Derrick Rossi, PhD

Founder, Moderna Therapeutics

Plenary Discussion

Tony Coles, MD

Cerevel Therapeutics

Michelle McMurry-Heath, MD, PhD Biotechnology Innovation Organization

“Education is probably the most important aspect of every field. Having students tour the labs and see what's possible will give them a different lens to view their education and their choices.”

Bringing Her Creative Flair to Stem Cell Research

Meet Kay Unger N

“At first, I thought ‘I’m not a scientist – how could I help?’” she added. “But Susan [Solomon, NYSCF CEO] assured me that my energy and creativity might be able to provide perspective on how to engage people like me: those who aren’t scientists but want to make a difference. I joined the Board last year and have loved it ever since.”

YSCF Board Member Kay Unger may be best known for her eponymous brand and trailblazing career in fashion, but she’s also an inspiring advocate for biomedical research, bringing fresh perspective and innovative ideas to NYSCF’s Board as we push the most promising science forward. Like many members of the NYSCF community, Kay’s life has been touched by disease, and she has responded by becoming an ardent supporter of advanced medical research.

Kay strongly believes in the power of education and mentoring, and she hopes that exposing students to STEM early on will help build a strong scientific workforce for the future. “I think education is probably the most important aspect of every field, especially for young students,” she remarked. “I have such smart grandkids, and I want to expose them to science when they’re 7 or 8 so that they can understand the change they could make in the world and possibly discover a passion for it. Having students tour the labs [as NYSCF often does] and see what’s possible will, I think, give them a different lens through which to view their education and their choices."

“My mom had macular degeneration, which is hereditary, and so I thought that perhaps it would be something that would affect me or my brother,” she said. “I also had cancer when I was 16 years old, which definitely changed my life, and my family has been affected by Alzheimer’s and diabetes.”

NYSCF Research Institute Named One of Four New Biotech R&D Facilities by NYC

he New York City Economic Development Corporation (NYCEDC) recently announced their investment in four new biotech research and development facilities, including the NYSCF Research Institute. This grant will allow NYSCF to purchase critical new equipment for drug discovery efforts and studies into diseases such as Alzheimer’s, diabetes, cancer, and more. “New York City’s prioritization of the life sciences has not only delivered thousands of new jobs and fostered tremendous innovation, it has also yielded meaningful scientific progress, developing hundreds of new cures and treatments,” said Rep. Jerry Nadler. “I am thrilled that the City has decided to continue these fruitful efforts by investing millions in organizations like Columbia University and The New York Stem Cell Foundation, whose work seeks to better prepare our city for future health emergencies and overcome current crises, including COVID-19.”

The NYSCF Research Institute Laboratories

NYSCFNEWSupdate

The Poetry of Science At the end of NYSCF’s annual Innovators Retreat (typically held in Montauk, New York, but conducted virtually the last two years), the graduating class of NYSCF – Robertson Investigators gives a toast. However, this year’s class (Drs. Claire Wyart, Maria Barna, Malin Parmar, Maria Lehtinen, Takanori Takebe, and Michael Yartsev) channeled their inner artist for a special poem inspired by their time in the program, from their first call with NYSCF CEO Susan L. Solomon informing them of the award to their final days at the retreat. Here’s a snippet:

NYSCF. It starts with a sound. The voice of Susan over the phone. And like all sounds, it has form. It changes your path and inspires a new voyage. Chance emerges from the depth of one’s dreams. At each retreat, minds come together. The patterns merge and merge more. It isn’t just beautiful music that is made all together, but a new vision. Together, a new scientific tribe woven from laughter, understanding, and trust. Susan, from the bottom of our hearts,

we thank you.

kiitos.

tack.

‫הדות‬.

(Dr. Barna in English)

ありがとうございます. (Dr. Lehtinen in Finnish) (Dr. Takebe in Japanese)

merci.

(Dr. Parmar in Swedish) (Dr. Yartsev in Hebrew) (Dr. Wyart in French)

For your trust, inspiration, leadership, and vision. And for the lesson that there is always hope and causes to fight for.

Susan L. Solomon Named to City & State’s ‘Life Sciences Power 50’ NYSCF CEO Susan L. Solomon, JD, was recently named as one of City and State’s ‘Life Sciences Power 50’ for her visionary leadership of The New York Stem Cell Foundation and its contributions to the growing life science sector of New York City.

“New York is a hub for groundbreaking life science research, and I am proud that NYSCF plays a critical role in this exciting growth. Sixteen years ago, NYSCF was a dream, a plan, and two lab hoods. Now, we employ over 100 talented scientists and staff in a 64,000-square-foot research institute, where we are developing the essential technology and translational research necessary to reach cures for the major diseases of our time.” -Susan L. Solomon 4

Learn From Experts About the Latest in Stem Cells, Neurodegeneration, COVID-19, and More Visit us at NYSCF.ORG/EVENTS

This spring, we gathered experts in COVID-19, rare diseases, age-related macular degeneration, multiple sclerosis,

Stanley Chang, MD, Columbia University, on NYSCF’s cell therapy for age-related macular degeneration “Stem cell treatments offer the possibility of actually improving vision for age-related macular degeneration patients. I think NYSCF’s therapy offers the opportunity to really change the way we can treat these patients, because the late stages of macular degeneration can really cause people to lose their ability to function, socialize, and recognize people.”

Parkinson’s, and more to share their stories and hopes for the future of precision medicine. Read more highlights and watch the full discussions at link above.

NYSCF – Robertson Stem Cell Investigator Alumnus Deepta Bhattacharya, PhD, University of Arizona, on COVID-19 vaccines “[Both Moderna and Pfizer vaccines] reported efficacies of about 95% for preventing symptomatic disease relative to the unvaccinated placebo cohort, which is pretty remarkable. 94-95% efficacy is right up there with the best vaccines we’ve ever seen. This is as good as it gets."

Teresa Wright Johnson, Lyfebulb Patient Ambassador, on her journey as a multiple sclerosis patient advocate “I am very hopeful for the future. Every day is not a good day, but every day that I’m here means that something great can happen. And my hope as a patient is to one day see a cure, but also to let people know that they aren’t alone, that their experiences matter, their life matters, and their voices matter.”

NYSCF Board Member Siddartha Mukherjee, MD, DPhil, Columbia University, on addressing vaccine hesitancy

Lorenz Studer, MD, Memorial Sloan Kettering Cancer Center, on new avenues for treating Parkinson’s disease

“What we haven't done very effectively is reach community groups that are especially resistant. And we have to find out who's trusted in those groups, and then approach those people to become ministers, if you will, of bringing more people to vaccination.”

“I would argue that aspects of aging may be reversible, and stopping or slowing down the aging process in our cells might be helpful not only for Parkinson’s disease, but possibly for all neurodegenerative or age-related diseases.”

Matt Wilsey, Grace Science Foundation, on his partnership with NYSCF to advance research into the rare pediatric disease NGLY1 Deficiency, which affects his daughter

Jordan Goldberg, The NYSCF Research Institute, on his advice to students interested in pursuing STEM

“Partnerships with places like NYSCF are super important to keep working with the parents and the advocates who are pushing forward. And there’s a lot of hope in our world for NGLY1 Deficiency now because of collaborations like this.”

“Just getting yourself into a laboratory is really important. And it doesn’t have to be in the exact role that you think you want to do for the rest of your life, but experiencing that environment is informative, and so is asking questions and being open to learning new things.”

Meet the 2021 NYSCF – Druckenmiller Fellows The NYSCF – Druckenmiller Fellowship was created to support young postdoctoral researchers in their pursuit of innovative stem cell research and is the largest dedicated stem cell fellowship program in the world. Fellows receive an annual stipend as well as support for their research, and are welcomed into NYSCF’s greater Innovator Community.

Julian Meyer Berger, PhD Columbia University

Peter M.J. Quinn, PhD Columbia University

Yulia Shwartz, PhD Harvard University

Dr. Berger is characterizing a new role for bone cells in hormone regulation.

Dr. Quinn is aiming to understand drivers of childhood retinal diseases.

Dr. Shwartz is exploring and optimizing wound healing in aging skin.

NYSCFNEWSupdate

Hair Falling Out From Stress? Resting Stem Cells Point to Why

Innovator Community Updates

We’ve all heard of – or experienced – hair loss due to stress. But what is it about extra anxiety that makes our hair flee our scalps? It turns out that chronic stress impairs hair follicle stem cells, leading to hair loss, according to a study in Nature by NYSCF – Robertson Stem Cell Investigator Ya-Chieh Hsu, PhD, of Harvard University. This research pinpoints a way in which stress affects the body – specifically our hair – opening the door for better understanding of the broader effects of stress and how to mitigate them.

Stem Cell Models Reflect the Intricacies of an Alzheimer's Brain There are no effective treatments for Alzheimer’s disease (AD), in large part because we do not understand how patient brain cells malfunction and die.

Mouse hair follicle | Image: Hsu Lab

How the Soldiers of the Skin Protect Us from Infection

Neurons created from the stem cells of 53 deceased individuals representing the spectrum of brain aging from healthy to AD show the same hallmarks as the actual brain tissue from these individuals, finds a new study in Neuron by NYSCF scientists including Scott Noggle, PhD, and led by Tracy Young-Pearse, PhD, of Harvard Medical School and Brigham and Women’s Hospital.

Our skin serves as an important barrier between us and the outside world, preventing a large array of possible infections from harming us. But how exactly does the skin mount this defense? The skin protects us from infections by stationing ‘sentinel’ immune cells at regular intervals across its outermost layer and repositioning these cells as needed to guard vulnerable areas, finds a new study in Nature Cell Biology led by NYSCF – Robertson Stem Cell Investigator Alumna Valentina Greco, PhD, in collaboration with NYSCF – Druckenmiller Fellow Alumnus Sangbum Park, PhD, and NYSCF – Druckenmiller Fellow Katie Cockburn, PhD. This study illuminates how different cell types in our body coordinate with the immune system to defend us from external threats like infections.

“This study demonstrates that these cells can be used to gain insights into disease progression and test drugs,” said Dr. Noggle. “The bank of cells will also be made available to the wider research community to enable powerful science.” Illustration credit: Kiran Pearse

A Surprising New Solution For Low Oxygen: Breathing Through the Rectum

Skin-resident immune cells actively coordinate their distribution with epidermal cells | Image: Greco Lab

Could COVID-19 Cause Diabetes?

Patients suffering from lung failure are often put on ventilators, but as we have seen during the COVID-19 pandemic, these tools aren’t always readily available and can run out.

COVID-19 affects more than just the lungs – it appears to be interfering with pancreatic beta cells (those affected in type 1 diabetes) as well. New research published in Nature and featured in National Geographic from NYSCF – Robertson Stem Cell Investigator Alumna Shuibing Chen, PhD, of Weill Cornell Medicine in collaboration with National Institutes of Health Director Francis Collins, MD, PhD, discovered that the SARS-CoV-2 virus can infect pancreatic beta cells and interfere with their ability to produce insulin or kill them off, similar to diabetes. Further studies will investigate how the virus reaches the pancreas and what role the immune system might play in the resulting damage.

A new technique involving ‘breathing through the rectum’ via a suppository containing oxygen seems to be a surprisingly effective strategy for treating oxygen deprivation, finds a new study in mice and pigs published in Med by NYSCF – Robertson Stem Cell Investigator Takanori Takebe, MD, PhD, of Cincinnati Children’s Hospital and Tokyo Medical and Dental University. This work demonstrates the great potential of this new oxygen delivery system as a simple and scalable way to treat patients suffering from low oxygen.

Autopsy sample of pancreas from a COVID-19 patient. Red: SARS-CoV-2 viral antigen; Green: insulin; Blue: E-Cad; Gray: DAPI | Image: Dr. Shuibing Chen

Dr. Takebe's study featured on the cover of Med

NYSCFNEWSupdate

2021 Major Award Winners Derrick Rossi, PhD Princess of Asturia Award Moderna founder, NYSCF Board Member, and NYSCF – Robertson Stem Cell Investigator Alumnus Derrick Rossi, PhD, will receive the prestigious Princess of Asturia Award – a recognition given by the Crown of Spain – for his work developing the mRNA technology that fuels many COVID-19 vaccines. Previous Laureates include Nelson Mandela, Stephen Hawking, Jennifer Doudna & Emmanuelle Charpentier, Annie Leibovitz, Mary Beard, Martin Scorsese, David Attenborough, and 2020 NYSCF Stem Cell Hero and NYSCF Leadership Council Member Frank Gehry. “What makes it a really great honor for me is being among this distinguished company,” said Dr. Rossi. “It's humbling and exciting.”

Feng Zhang, PhD Stem Cell and Regenerative Medicine

Action Award

NYSCF – Robertson Stem Cell Investigator Alumnus Feng Zhang, PhD, of the Broad Institute of MIT and Harvard has recently received a Stem Cell and Regenerative Medicine Action Award from the Regenerative Medicine Foundation for his pioneering work in gene editing.

“Feng’s work has had an extraordinary impact, the kind of impact that only a handful of scientists can lay claim to,” said NYSCF CEO Susan L. Solomon, who introduced Dr. Zhang at the World Stem Cell Summit this June, where he accepted the award. “From his seminal role in creating the technology of CRISPR gene editing in human cells, to his numerous adaptations of this technology, Feng has changed the world.”

Marissa Scavuzzo, PhD Hannah H. Gray Fellowship Award from

The Howard Hughes Medical Institute

Marissa Scavuzzo, PhD, a 2019 NYSCF – Druckenmiller Fellow Alumna at Case Western Reserve University, is a recipient of the Hanna H. Gray fellowship award from The Howard Hughes Medical Institute. This fellowship aims to increase diversity in science and allows fellows the freedom to explore novel scientific territory and embrace their curiosity. “This opportunity will equip me to do cutting-edge science and to dive into the unknown, not only throughout my postdoc, but into my formative years as an independent research investigator,” said Dr. Scavuzzo. “It has been a dream of mine to lead a team of diverse scientists on expeditions to explore new biology, and this award makes that dream a reality.”

Catalyzing the Careers of Young Scientists NYSCF has always sought to cultivate young talent and inspire the next generation of scientists and thought leaders. We are proud to equip many budding scientists with experiences that will jumpstart the next phase of their careers, and we are excited to see the impact that these rising stars will have on the field of disease research. Hear from members of the NYSCF family who have moved on to graduate school about why they loved their time here.

“I always knew I loved research, but when I came to NYSCF and saw the different routes you can take in the stem cell field, it really solidified my decision to become a scientist.” “The most rewarding thing about my time here is the relationships I’ve built. I’ve made so many brilliant, motivating friends and have become a part of a strong scientific community. NYSCF really gave me a renewed sense of passion for science and inspired me to pursue my PhD.”

Camille Fulmore

PhD Student at University of California, Berkeley

“I really believe NYSCF is the best place to be a junior scientist. I feel so empowered here, and I have access to groundbreaking technologies and brilliant people.”

“Having worked in the lab for a while, I'd like to bridge the gap between the scientists and the people on the business side to help accelerate research.”

Lili Barbar

MD/PhD Student at Washington University in St. Louis

Katie Reggio

Jenna Hall

MBA Student at PhD Student at University of California, Los Angeles The University of Melbourne, Australia NYSCFNEWS update

Future cures begin with your support today!

Please make a gift to help NYSCF advance stem cell research toward the clinic. You can donate online at www.nyscf.org/donate or by mail to: The New York Stem Cell Foundation 619 West 54th Street, 3rd Fl, New York, NY 10019

619 W 54 th Street New York , NY 10019

Legacy of Cures Join our Legacy of Cures Society by including The New York Stem Cell Foundation in your will. Together, we can accelerate cures for the major diseases of our time. Your support will benefit generations to come. Please contact the Development team at (212) 365-7434 or legacyofcures@nyscf.org. Follow us on social media!

NYSCFNEWSupdate

the

NYSCF

GALA

Honoring Stem Cell Heroes

& Science Fair

Show Up for Science Virtual Celebration Directed by Scott Ellis Hosted by Sanjay Gupta, MD

Susan and Stephen Scherr

Victor Garber

for their longstanding leadership and support of NYSCF

for his advocacy for the patient community

Featuring Special Guests Annaleigh Ashford • Bob Balaban • Alec Baldwin Bradley Cooper • Anthony Fauci, MD • Santino Fontana Jennifer Garner • Whoopi Goldberg • Sean Hayes Jane Krakowski • Nathan Lane • Tony Shalhoub Martha Stewart • Jesse Williams

Watch the full program now at nyscf.org/gala

Derrick Rossi, PhD • Kizzmekia Corbett, PhD • Barney Graham, MD, PhD Katalin Karikó, PhD • Drew Weissman, MD, PhD for the critical research that led to the development of the COVID-19 Vaccines