NYSCF News Update: Vol 14, Issue 2

NEWSupdate

NYSCF

VOLUME 14 ISSUE 2: 2021-2022

The New York Stem Cell Foundation Research Institute

DRUG DISCOVERY IS GETTING AN UPGRADE Why do we so rarely hear about new drugs being discovered for diseases like Alzheimer’s, Parkinson’s, or multiple sclerosis? Read more about NYSCF’s latest approach to accelerate drug discovery with artificial intelligence. Pages 2&3

SHOWING UP FOR SCIENCE

REMEMBERING JACK GERNSHEIMER

FOSTERING EQUITY IN SCIENCE

SPEAKING YOUR MIND

Celebrities and Stem Cell Heroes join the NYSCF Gala

His legacy of kindness and advocacy

And more highlights of the NYSCF Conference

A new tool translates brain signals into speech

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DRUG DISCOVERY IS GETTING AN UPGRADE

“Traditional drug discovery isn’t working very well, particularly for complex diseases like Parkinson’s,” remarked NYSCF CEO and Founder Susan L. Solomon, JD. “Clinical trials fail at an astronomical rate.

This is because drug developers typically rely on mice, whose biology is completely different from humans, as well as preconceived notions about what is driving the disease, which are often incorrect or untrue for every patient.”

With NYSCF’s robotic systems for studying patient cells – The NYSCF Global Stem Cell Array – combined with the power of artificial intelligence, we have a new opportunity to dramatically improve the success of drug discovery. The potential of this platform was recently demonstrated in a Nature Communications study, published in collaboration with Google Research, successfully identifying new cellular hallmarks of Parkinson’s disease (PD) by creating and analyzing images of millions of skin cells from patients and healthy controls.

The platform works a bit like the face recognition technology that unlocks your smartphone. An artificial intelligence algorithm studies thousands of images of cells that have been generated by the Array and learns how to distinguish between those from healthy individuals and those with a disease. The more it learns, the better it gets at pinpointing characteristics of diseased cells.

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Daily scans of stem cells growing in a dish.

Image credit: Brodie Fischbacher

“Our platform was able to tell the difference between healthy cells and cells from Parkinson’s patients,” explained Daniel Paull, PhD, NYSCF's SVP of Discovery and Platform Development. “It could even pinpoint the exact donor that a given sample of cells came from. In Parkinson’s research, we often lack the tools to tease apart these minute differences, but here we were able to do just that.”

These algorithms are special because they are unbiased, meaning they don’t operate based on preconceived notions about what drives Parkinson’s disease. They take a more comprehensive approach to uncover entirely new features in areas that might be a surprise.

“Now that we have these signatures of Parkinson’s disease, we’ve started looking for drugs that reverse these signatures to make the cells healthy again,” said Dr. Paull. “We’re testing hundreds of drugs across different patients, since it’s likely that different patients will respond in different ways.”

NYSCF scientist Enya O' Connor on the Array ®

Parkinson’s is just the beginning – the team is already applying the platform to other diseases for which treatments are lacking, introducing an entirely new paradigm for finding drugs that actually work and can be tailored to certain patient groups.

“We’re already investigating a number of other diseases to see if we can similarly detect these disease signatures in those cells,” added Ms. Solomon. “We’ve needed a new drug discovery model for a long time, and the combination of NYSCF’s technology with very powerful artificial intelligence, in my opinion, is a home run.”

Top Image from left: Fibroblasts (cells found in connective tissue) generated by the Array ® and used to study PD

Learn more at nyscf.org/news

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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 David Rockwell Clifford Ross Kara Ross & Stephen Ross Andy Russell Susan & Stephen Scherr Ian Schrager Barbara Stovall Smith Martha Stewart David & Jane* Walentas John Whitehead* Dick Wolf *In Memoriam

Dear Friends, I started NYSCF because I believed that stem cells are our best hope to find new treatments for diseases affecting ourselves and our loved ones. As we begin the new year, I am more certain in this belief than ever. Here at the NYSCF Research Institute, we have made incredible progress using stem cells to understand the origins and progression of disease, test drugs on the actual cells affected in many disorders, and develop new therapies.

And there is so much more to come.

We are moving closer to a clinical trial using stem cells to replace the eye cells in patients who have lost their sight from age-related macular degeneration. This will be a transformative, and hopefully curative, therapy that may pave the way for many patients to regain their vision. While it has taken years of planning, and untold hours of scientific effort and discovery, including many collaborations, we are thrilled to make progress toward the clinic for such a cruel disease.

We also just published a study showing that we were able to distinguish who had Parkinson’s disease and who did not based only on the appearance of their skin cells (see Page 2). This radical new approach, combining artificial intelligence, advanced imaging, and stem cell biology, will pave the way for an entirely new system that uses NYSCF’s technology to find better drugs for countless diseases.

These are only two examples of the incredible progress being made at the NYSCF Research Institute every day. Adding in the outstanding work of the NYSCF Innovator community and the stem cell field at large, it is impossible not to be optimistic as we look to the future. As I look forward to the year ahead, I am thankful for everyone who makes our work possible. We are better positioned than ever to deliver on our promise to patients, and together, we will continue to pave the way for a brighter future.

With warm regards,

Susan L. Solomon, JD CEO and Founder

Innovator Community Updates How The Microscopic Residents in Your Gut Could Influence Cognitive Decline

He Lost His Voice in 2003— Now, Thanks to a Brain Implant, He’s Getting it Back

Your intestines are home to trillions of microbes that help you take in nutrients and maintain a healthy gut, and they are also known to interact with and influence brain function. This “gut-brain connection,” however, is not well understood.

For patients with paralysis or diseases that impact muscle movement such as ALS, Parkinson’s, or cerebral palsy, the lack of effective ways to communicate can be debilitating.

Gut microbes can affect the brain to speed cognitive decline in mice through accumulation of bacteria called Bilophila, finds a new study in Cell Host & Microbe by NYSCF – Robertson Neuroscience Investigator Elaine Hsiao, PhD, of UCLA. This study illuminates a possible role of gut microbes in cognitive decline and could inform new treatments or preventative measures against it.

An artificial intelligence-driven brain implant is helping a paralyzed man translate brain signals into speech. The study, led by NYSCF – Robertson Neuroscience Investigator Alumnus Eddie Chang, MD, of the University of California, San Francisco appears in The New England Journal of Medicine.

This work demonstrates the power of an exciting new technology to give patients a faster, more seamless way to communicate.

Left: Microbiota in the gut. Image credit: Alpha Tauri 3D Graphics/Shutterstock Middle: Patient during a session with researchers, including, from left, Dr. Chang, Sean Metzger, David Moses and Jessie R. Liu. Credit: Mike Kai Chen for The New York Times Right: Dr. Vermeulen

A New Stem Cell Approach to Cancer Prevention, Straight From the Gut Colon cancer is responsible for the second highest number of cancer deaths in the United States, and third highest worldwide. The majority of cases are thought to be caused by mutations in a gene called APC that causes intestinal stem cells to overpower neighboring unmutated ones, leading to uncontrolled growth and tumor formation. It has remained unclear how exactly these mutated stem cells outcompete their healthy counterparts.

APC-mutant cells release harmful molecules that interfere with healthy stem cells and allow mutated ones to overwhelm them, shows a Nature study led by NYSCF – Robertson Stem Cell Investigator Louis Vermeulen, MD, PhD, of Amsterdam University Medical Center. The team also found that lithium, commonly prescribed for psychiatric conditions, can prevent tumor formation caused by APC-mutant stem cells in mice. This work has led to a new clinical trial to test whether lithium drugs can prevent colon cancer in genetically predisposed patients.

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SHOWING UP FOR SCIENCE Highlights of the NYSCF Gala

Jane Krakowski and NYSCF's Dr. Scott Noggle teach about stem cells

On October 5th, celebrities, scientists, and supporters ‘showed up for science’ at the The 2021 New York Stem Cell Foundation Gala and Science Fair.

Again hosted by CNN’s Chief Medical Correspondent Sanjay Gupta, MD, and directed by Tony Nominee Scott Ellis, the Gala featured the latest updates and breakthroughs in stem cell research, bringing the world of the NYSCF Research Institute laboratories to life via a multi-platform digital experience.

“As we’ve seen throughout this past year and a half, the pursuit and success of cutting edge medical research is ubiquitously urgent for the entire world,” remarked Dr. Gupta. “And as we continue to navigate this pandemic, science offers us so much hope for tackling so many of today’s challenges as well as the unknowns of tomorrow: not just COVID-19, but all of the diseases that affect us and our loved ones.”

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The event also paid tribute to Stem Cell Heroes ​​Susan & Stephen Scherr for their longstanding leadership and support of NYSCF, Victor Garber for his advocacy for the patient community, and Derrick Rossi, PhD; Kizzmekia Corbett, PhD; Barney Graham, MD, PhD; Katalin Karikó, PhD; and Drew Weissman, MD, PhD for the critical research that led to the development of the COVID-19 vaccines – also recognized as TIME’s 2021 Heroes.

Watch the star-studded program at nyscf.org/gala

Hear from Jane Krakowski, Jennifer Garner, Bradley Cooper, Martha Stewart, Tony Shalhoub, Jesse Williams , and others to learn how NYSCF uses stem cells to better understand disease, discover new and better drugs, and accelerate research towards cures.

Top Row f Second Row Third Row from Left: Last Row

from Left: Susan & Stephen Scherr with family, Victor Garber from Left: Drs. Sanjay Gupta, Derrick Rossi, Kizzmekia Corbett : Drs. Barney Graham, Katalin Karikó, Drew Weissman, Anthony Fauci from Left: Jennifer Garner, Bradley Cooper, Martha Stewart, Tony Shalhoub, Jesse Williams

Remembering

Jack Gernsheimer We are deeply saddened by the passing of 2015 Stem Cell Hero Jack Gernsheimer. Jack was not only a fierce advocate for stem cell research, he was a direct contributor to path-breaking research into Parkinson’s disease.

In 2014, the NYSCF Research Institute published a study describing the unexpected molecular differences in brain cells derived from induced pluripotent stem cells made from Jack and his identical twin brother, Jeff, who does not have Parkinson’s.

Jack’s selfless and eager participation in research has helped move the entire field closer to understanding the complex interplay of genetics and environment on a complicated and devastating disease. His passion and kindness uplifted everyone around him, including all of us at NYSCF. He will be deeply missed.

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Translating Discoveries into Medicine, Advancing Equity in Science, and New Cancer Therapies Highlights of the NYSCF Conference | Watch select talks at

youtube.com/NYSCF

On October 19th and 20th, the 2021 NYSCF Conference convened over 600 researchers, physicians, and thought leaders to share their latest findings in translational stem cell research and discuss key challenges and opportunities to accelerate the path of regenerative medicine therapies to patients.

“What we learned over this last year and a half is that science is fast – faster than we ever dreamed possible, and that the major barriers that remain between where we sit today and better innovations for patients are mostly political and social, not scientific,” said Michelle McMurry-Heath, MD, PhD, President & CEO of Biotechnology Innovation Organization, in the plenary discussion on translational research with NYSCF’s CEO Susan Solomon and CEO of Cerevel Therapeutics Tony Coles, MD.

The Road Ahead for Translational Research

The meeting, held virtually for the second consecutive year, also featured an insightful panel discussion on how to advance the values of diversity, equity, inclusion, and belonging (DEIB) in the scientific workforce. Panelists underscored the factors that have led to a lack of diversity in the STEM community, raised awareness of the unique challenges faced by systematically marginalized groups, and highlighted ongoing efforts for change.

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Fostering Diversity, Equity, Inclusion, and Belonging in STEM

“We need to act on multiple levels,” said Valentina Greco, PhD, Vice Chair of Diversity, Yale University Department of Genetics. “First, the top leadership needs to invest in their own education; second, multiple lenses have to be present at the table when a decision is made; and lastly, we need to scrutinize each and every single decision we make.”

Several speakers shared exciting stories of taking their discoveries to the clinic, such as creating functional insulin-producing pancreas cells and using stem cellderived neurons to treat Parkinson’s disease. The meeting also highlighted new avenues for cancer treatment, including cancer vaccines, combination therapies to overcome resistance, and NYSCF’s own efforts to advance precision oncology research and drug testing.

Moderna Therapeutics founder Derrick Rossi, PhD, (also a NYSCF – Robertson Investigator Alumnus and NYSCF Board member) delivered the keynote lecture where he shared his story of bringing mRNA technology from a lab discovery to a flourishing biotech that has provided vaccines for millions worldwide.

Keynote Lecture: Stem Cell Science and New Therapeutic Strategies

Meet the 2021 NYSCF — Robertson Investigators At the NYSCF Conference, we announced our 2021 class of NYSCF – Robertson Investigators, welcoming six outstanding early career stem cell researchers and neuroscientists into the NYSCF Innovator community. The NYSCF – Robertson Investigator Awards provide critical seed funding – $1.5 million over five years – to scientists who have recently established independent laboratories.

Shruti Naik, PhD New York University Grossman School of Medicine Dr. Naik studies the crosstalk between stem cells, immune cells, and microbes to develop better treatments for inflammatory conditions like psoriasis and cancer.

Annegret L. Falkner, PhD Princeton Neuroscience Institute Dr. Falkner’s lab examines how social experiences, including social dominance and defeat, change brain circuits and alter information flow to impact behavior.

Alex Pollen, PhD University of California, San Francisco Dr. Pollen is studying what makes our brains uniquely human, by comparing how genes behave in stem cell models from great apes vs. humans.

Junjie Guo, PhD Yale University School of Medicine Dr. Guo is developing and applying new tools to investigate how genes in neurons are regulated and the implications for neurodegenerative diseases.

Jun Wu, PhD UT Southwestern Medical Center Dr. Wu develops strategies towards growing functional, transplantable human organs in animal hosts.

Lauren Orefice, PhD Massachusetts General Hospital Dr. Orefice’s lab studies how sensory processing is altered in developmental disorders, including autism spectrum disorder.

NYSCF CONFERENCE

THE ROCKFELLER UNIVERSITY, NEW YORK

Keynote Speakers

Janet Rossant, PhD, FRS, FRSC

University of Toronto

Feng Zhang, PhD

OCTOBER 18 - 19, 2022

Massachusetts Institute of Technology

Education and Outreach Read highlights and watch the full discussions at

nyscf.org/events

Alzheimer’s, Stem Cells, and the Aging Brain A study by NYSCF scientists and collaborators reveals the power of stem cell models for capturing features of aging brains in a continuum from healthy to severe Alzheimer’s disease. Experts recently discussed what their latest findings tell us about the cells in our aging brains, the genetic factors that may be driving cognitive decline, and the road toward effective treatments.

Drs. Tracy Young-Pearse, David A. Bennett, Raeka Aiyar, and Scott Noggle; Susan L. Solomon

“Some of the cells collected from patients in this study were frozen since the early nineties, and I’m not sure anybody besides NYSCF could have actually brought them back to life. NYSCF has developed a really strong pipeline to rejuvenate these cells and make them into stem cells.” - Dr. Young-Pearse

High School Students Explore the World of Stem Cells For 47 high school students, a deep dive into the many facets of STEM as part of the 2021 NYSCF Stem Cell Research Immersive Experience is helping them discover a passion for science. The program, a one-week intensive course, featured talks from NYSCF scientists, career panels, professional development exercises, and plenty of opportunities for questions and discussion.

High school students join for the Immersive, August 2021

“I like that NYSCF creates opportunities like this program to expose students to stem cell research, and that they focus not just on the science, but on social aspects like gender equality as well.” - 2021 Summer Immersive Student

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Education and Outreach

Gene Editing and Careers in STEM

Dr. Josephine Wesely

Gene editing is an exciting field with enormous potential to help researchers improve our understanding of gene function and develop ways to potentially treat and cure a range of diseases.

In December, students gathered for a webinar where NYSCF Principal Scientist in Functional Genomics Josephine Wesely, PhD, shared how NYSCF uses gene editing in the lab to unlock the secrets of disease and shared about her own journey as a scientist and patient.

“There are actually therapies now – for example, for sickle cell anemia – that apply gene editing to give patients a better life. As a type one diabetic, I’m hopeful for a cell transplant for myself in the future. It’s really encouraging to see how the field is moving really fast in the right direction.” - Dr. Wesely

Summer Interns Learn About Stem Cells and Themselves For the nineteen students interning at NYSCF last summer, the experience was unlike any internship they’ve had before. Whether it was working hands-on in the lab to conduct disease research or contributing to a variety of NYSCF’s projects in communications, business development, legal, and more, our interns expressed that they learned a lot and made a real difference for their team.

Intern Matt Weiss speaks with NYSCF scientist Kiran Ramnarine, MS

“My previous internships have been in university labs, and what was different here was the amount of collaboration that I saw between groups, between teams, and between scientists.” -Matt Weiss, University of Michigan

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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 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.

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NYSCFNEWSupdate

2022 Spring Events Calendar The NYSCF Academy for Science and Society provides comprehensive scientific education for individuals of all ages, backgrounds, and scientific understanding who want to enable progress.

Join us at nyscf.org/events

Stem Cells: The Future of Medicine

February 2 Recording available!

Dr. Scott Noggle

Watch now at nyscf.org/events

Unlocking New Brain Disease Treatments with Artificial Intelligence

February 16 Recording available!

Dr. Vikram Khurana, Leena Panwala, Dr. Daniel Paull

New Hope and Equity for Women’s Reproductive Cancers

March 2 Virtual, 4:00 PM

Drs. Ursula Matulonis, Sohrab Shah, and Laura Andres-Martin

We are grateful to the Stavros Niarchos Foundation (SNF) for their support of our education and outreach programs.