Yasmin Hurd, PhD: Asking the Questions No One Was Asking

Yasmin Hurd, PhD: Asking the Questions No One Was Asking

A couple of decades ago, most people familiar with cannabis called it marijuana—and had probably never heard of cannabidiol (also known as CBD), one of its components.

Today, many people have heard about CBD and its potential therapeutic uses thanks to the work of Yasmin Hurd, PhD, Ward-Coleman Chair of Translational Neuroscience and Director of the Addiction Institute of Mount Sinai, who pioneered research into the compound, cannabis more generally, and their various interactions with substance-use disorders.

“I believe I had been asking questions that no one was asking at the time,” said Dr. Hurd. Her work helped her get elected to the National Academy of Sciences (NAS) in May. She is also a member of the National Academy of Medicine.

Dr. Hurd’s research focuses on the neurobiology of drug addiction and various psychiatric disorders, spanning both basic science research and translational work in humans. Having evidence in both non-clinical and clinical settings has helped the research be applicable in guiding treatment and health policy, she said.

Producing research that actually has impact to our society was important to me,” Dr. Hurd said. Through her work in studying molecular impacts of exposure to substances from prenatally to adulthood, including pioneering studies of the human brain, she discovered milestones about the developmental and transgenerational effects of exposure to cannabis, and also its therapeutic potential for treating other forms of addiction, such as with opioids.

“At the time no one knew what cannabidiol was, and today you can even see it being added to coffee in coffee shops,” she said with a laugh.

Dr. Hurd was elected to the National Academy of Sciences along with Helen Mayberg, MD, founding Director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai. Read more about Dr. Mayberg’s achievements here.

The Potential of a Limitless Environment

More than a decade ago, in the field of medicine, marijuana was still seen as having limited evidence for being a treatment for any condition and many thought that it was a benign drug without long-term impact on the brain. “My research into the developmental effects of cannabis as well as potential therapeutic aspects of cannabidiol made people take another look at cannabis and have shaped the questions people are asking today,” she said.

Being able to ask the questions that no one was asking requires the combination of the researcher’s driving instinct and institutional support. “I think Mount Sinai helped me to not only ask, but to answer those questions,” Dr. Hurd said.

“Physicians had always focused on treating the adult patient in front of them, but the thinking about what had brought them there in the first place was unaddressed,” she said. As she studied adults with substance-use disorders, she found many had drug exposures early in life, and sought to understand whether those early exposures were linked to psychiatric illnesses later on as adults.

Dr. Hurd recalled that when she joined Mount Sinai in 2006, she pitched ideas about advancing her preclinical work into humans to Dennis Charney, MD, Anne and Joel Ehrenkranz Dean of Icahn Mount Sinai and President for Academic Affairs of the Mount Sinai Health System. She had begun to study how cannabidiol worked in animal models but had not yet investigated it in live human beings. “Dean Charney said, ‘You could absolutely do that here,’ and just knowing that was possible enabled me to run clinical trials.”

“Early in my career, I never thought that my research would evolve the way it has,” Dr. Hurd said. “Instead of being theoretical about translation, I actually got to study it in humans.”

“The whole thing about being in an environment where there are no limitations placed on you is that it becomes dependent on your drive, on the questions you want to ask,” Dr. Hurd said. “I remember going away from that meeting feeling happy, thinking, ‘Whoa, there are no limits. What do I really want to do now?’”

Even today, that is a question Dr. Hurd asks herself. A constant in her research is for her work to always reveal something relevant to the human condition. As she advanced her work in addiction, she has come to understand that addiction is more a disorder of epigenetics, in contrast to a disease of genetic inheritance.

“Our next phase, especially in medication development, is to see if we can leverage the knowledge about epigenetic dysregulation to develop targeted interventions to reverse addiction,” Dr. Hurd said.

Addressing the Future of Addiction Research

Epigenetic changes are reversible, and this gives rise to hope that addiction ultimately can be, too. “When I started in this field, there was the pervasive stigma of the common phrase ‘Once an addict, always an addict,’” she said. “After studying this for such a long time, I know it’s not true. The effects may be long-lasting, but they are not locked for perpetuity.”

The road ahead will be challenging. Some challenges are merely logistical, such as space issues for animal and clinical research. Others are more systemic. “Those problems I face today remain the same I had at the start of my career,” Dr. Hurd said. “Getting grant money is still challenging, especially for high-risk projects. Stigma still surrounds addiction, even within science.”

Addressing the stigma will help with securing funding. They’re linked, Dr. Hurd said. “But with good support, I believe I’ll get there.”

A closer look at Dr. Hurd’s work

Dr. Eric Nestler

Eric Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director of The Friedman Brain Institute, Dean for Academic Affairs of Icahn Mount Sinai, and Chief Scientific Officer for the Mount Sinai Health System, discusses how Dr. Hurd’s work, which comes from asking basic questions, can translate into helping patients.

“Yasmin has always put a premium on mining the results of her work in rats to devise a new understanding for how substances affect humans and also to develop new treatments,” Dr. Nestler said.

Membership of the National Academy of Sciences—considered one of the highest honors for a scientist—comes through election by existing members only. Candidates’ entire bodies of work and contributions to the field are considered as part of the nomination process and their entries are voted on in April each year, with a maximum of 120 U.S. citizens and 30 non-citizens elected annually, according to NAS. There are currently approximately 2,400 U.S. members and 500 international members, of whom 190 have received Nobel prizes. Mount Sinai has six current faculty in the prestigious organization.

Her recent work on epigenetic changes that marijuana causes in the brain and that can be passed across subsequent generations has considerable importance to society, Dr. Nestler said. That paper on epigenetic changes, published in 2021 in the Proceedings of the National Academy of Science, discussed how children from mothers who used cannabis during pregnancy showed higher anxiety, aggression, hyperactivity, and levels of the stress hormone cortisol, compared to children of non-cannabis users.

“As marijuana is increasingly legalized, many people think of marijuana as being extremely safe,” Dr. Nestler said. “Yasmin has shown clearly that it may not be so safe, especially in pregnant women.”

Dr. Hurd’s research on the intersection of cannabinoids and addiction has significant impact too, Dr. Nestler said. Notable publications include her paper, published 2017 in Trends in Neurosciences, that laid out animal model evidence of cannabidiol, a non-high-producing compound derived from cannabis, as a treatment for opioid addiction because it lowers the reward for opioid use.

“That led her to launch a clinical trial that is funded by the National Institute on Drug Abuse,” Dr. Nestler said, referring to the agency that’s part of the National Institutes of Health. “This is a major milestone for Dr. Hurd’s research program and for the field at large.”

Mount Sinai Launches Center for Engineering and Precision Medicine: What Is it and Why Does it Matter?

Shirley Ann Jackson, PhD, President of Rensselaer Polytechnic Institute, Priti Balchandani, PhD, and Jonathan Dordick, PhD, attend the launch of the Center for Engineering and Precision Medicine.

The opening of the Center for Engineering and Precision Medicine (CEPM) brings together biomedical experts from the Icahn School of Medicine at Mount Sinai and engineering experts from Rensselaer Polytechnic Institute under the same roof.

The center, located on the West Side of Manhattan, represents a first in the city that would bring together two areas of research that greatly benefit from joint development: engineering and precision medicine. The center’s co-directors, Priti Balchandani, PhD, Professor of Diagnostic, Molecular and Interventional Radiology, Neuroscience, and Psychiatry at Icahn Mount Sinai, and Jonathan Dordick, PhD, Institute Professor of Chemical and Biological Engineering at Rensselaer, explain why this center is a big deal.

What is precision medicine?

Dr. Balchandani: With every patient being unique, diseases can sometimes occur differently across individuals. Precision medicine is a term meant to describe customized health care tailored to a specific group of patients. In order to do that, we need to apply new technologies engineered to understand causes of specific diseases and combine highly precise and sensitive physiological measurements to provide targeted treatment plans.

There are many areas in which precision medicine plays a big part. Cancer is one of them, as are various neurodegenerative diseases, such as Alzheimer’s disease, where having precise tools to measure and integrate different types of patient data is crucial not just to the development of tailored treatment plans, but also for understanding disease mechanisms.

If [engineers] are at the table at every stage of research, they can figure out the best solutions rather than look for what exists out there.

Dr. Jonathan Dordick

Co-Director of CEPM; Institute Professor of Chemical and Biological Engineering at Rensselaer Polytechnic Institute

How have precision medicine and engineering developed in the past?

Dr. Dordick: I wouldn’t say they were siloed, but advancements in either field have sometimes developed alongside each other, or on top of each other, rather than being fully integrated.

For example, devising a therapeutic at a broad level is a traditional path toward patient treatment, but then what are the ways and tools needed to individualize the treatment for an individual patient? How do we scale those methods? Engineering brings in infrastructure, such as using modeling or simulations, as well as broad systems-level expertise that can sometimes help answer those questions.

But there hadn’t really been a case where engineers and biomedical researchers got together to ask those questions from the get-go and figure out what tools might be needed. If they are at the table at every stage of research, they can figure out the best solutions rather than look for what exists out there.

What sort of innovation might this center enable?

Dr. Balchandani: Types of innovations include devices, algorithms, methods, and therapeutics to improve diagnosis, treatment, and surgical care of a wide range of diseases, including neurodegenerative disease, infectious diseases, and cancer.

There will be a mix of basic science and translational work. For example, the basic science work may be focused on revealing disease causes or mechanisms in order to drive new treatments. These preliminary clinical trials are important to establish safety and eventually help treatments receive regulatory approval.

Dr. Dordick: A co-located center in New York City primes us to answer pressing questions. Take COVID-19, for example: Why did some people develop severe disease while others didn’t? What are the mechanisms that lead to long COVID? Through the combined expertise of Rensselaer and Mount Sinai, we hope to learn answers at an individual level about this pandemic, which will make us better prepared for future crises.

I also envision us making strides in improving current therapeutics. Can we devise less invasive techniques for certain treatments? Can we better grow tissue that reduces the risk of rejection? Rensselaer is not a medical school, and through this partnership we’ll be able to know what are the right questions to ask.

Read more about what the new Center will focus on and its future plans

Our hope is that they will be designed with the intention of being tested in clinical trials immediately after development.

Dr. Priti Balchandani

Co-Director of CEPM; Professor of Diagnostic, Molecular and Interventional Radiology, Neuroscience, and Psychiatry at Icahn Mount Sinai

How soon can these innovations reach patients?

Dr. Balchandani: Our hope is that they will be designed with the intention of being tested in clinical trials immediately after development. We will also work with commercial partners to manufacture and deploy the inventions to patients as quickly as possible. We will create a “development lab” within the Center to facilitate this.

New Center for Engineering and Precision Medicine Paves the Way for Two Fields to Work More Closely Together

Shirley Ann Jackson, PhD, President of Rensselaer Polytechnic Institute, Eric Nestler, MD, PhD, Director of The Friedman Brain Institute, and Andrew Kimball, president of the New York City Economic Development Corporation, sign a ceremonial agreement at the launch of the Center for Engineering and Precision Medicine.

The Icahn School of Medicine at Mount Sinai and the Rensselaer Polytechnic Institute on May 12 announced the opening of the Center for Engineering and Precision Medicine (CEPM), forming a new venture to bridge engineering and biomedical science expertise between the two organizations.

The center, located at 619 West 54th Street in Manhattan, focuses on three research areas—neuroengineering, immunoengineering, and regenerative and reparative medicine. Its footprint includes spaces for wet and dry laboratories, as well as offices for faculty and researchers.

In addition to research, CEPM will develop a joint PhD in engineering and precision medicine, and ultimately master’s degrees and certificate programs. Enrollment could occur as early as the fall of 2023, said Jonathan Dordick, PhD, Institute Professor of Chemical and Biological Engineering at Rensselaer and Co-Director of the Center.

The Center is the latest development borne from a partnership between Mount Sinai and Rensselaer—dating to 2013—that has secured more than $70 million in shared research funding. Milestone achievements have included an artificial pancreas system developed by the two institutions and a number of advances in improving treatment and health infrastructure during the COVID-19 pandemic.

“We identified that there was a need in New York City and the state for such a collaboration to be the foundation of a new path of innovation between engineering and precision medicine,” said Priti Balchandani, PhD, Professor of Diagnostic, Molecular and Interventional Radiology, Neuroscience, and Psychiatry at Icahn Mount Sinai and Co-Director of the Center.

FAST FACTS

  • Project planned since: 2018
  • Footprint: 14,000 usable square feet
  • Faculty size: Mount Sinai and Rensselaer jointly hope to recruit 20 faculty members within five years for the center
  • Planned academic programs: PhD in Engineering and Precision Medicine jointly awarded by Mount Sinai and Rensselaer, master’s programs, and certificate programs in entrepreneurship and other areas relevant to advanced education at the interface of medicine and engineering.

The creation of the Center sets the stage for engineers to consider the needs of biomedical researchers to develop tools, systems, and infrastructure needed to address unanswered questions, Dr. Dordick said. “As a field, we’ve been asking how engineering can play a closer role at each stage of development in biomedical science from bench to bedside.”

Read a Q&A from the leaders of the new Center on how bridging engineering and precision medicine can benefit patients

The Center will also serve as a hub for industry partners and collaborators. Its “Development Labs” will be working with Mount Sinai Innovation Partners, the team focused on commercializing innovations from Mount Sinai Health System, on technology transfers with industry partners, as well as fostering the creation of startups, Dr. Balchandani said.

“This partnership with Rensselaer is truly a first where not only are two organizations coming together for research and academic excellence,” she noted, “it is also creating a partnership that will augment translational work in the city.”

Mount Sinai is also growing its presence in the area by building laboratory spaces in a facility on 11th Avenue, adjacent to the Center, for the Mount Sinai West campus.

“Ultimately, the goal is to develop new innovations that will benefit patients,” Dr. Dordick said. “The work at the Center cannot start soon enough.”

SARS-CoV-2: Three Leading Microbiologists Discuss the Path Forward

From left: Florian Krammer, PhD, Adolfo García-Sastre, PhD, and Peter Palese, PhD

Microbiologists at the Icahn School of Medicine at Mount Sinai, who created the first and most reliable test to determine whether an individual has antibodies to SARS-CoV-2, have been monitoring the virus since it began circulating in Wuhan, China, in late 2019.

Now, Peter Palese, PhD, Horace W. Goldsmith Professor and Chair of the Department of Microbiology, and Florian Krammer, PhD, Mount Sinai Professor in Vaccinology— weigh in on the future of SARS-CoV-2 and its place in our lives. They, and their colleague, Adolfo García-Sastre, PhD, the Irene and Dr. Arthur M. Professor of Medicine, recently created a low-cost COVID-19 vaccine that can be manufactured wherever influenza vaccines are made—particularly in low-and-middle-income countries. The scientists are also working on a universal flu vaccine, which would confer immunity without having to be administered annually.

As we move away from this pandemic will SARS-CoV-2 continue to play a large part in our lives?  

Dr. Palese: Clearly the future is difficult to predict, but one likely scenario would be similar to the way we manage influenza viruses, which necessitates continuing vaccinations as we go into the future—perhaps once a year or once every two years. In this case, the virus continually changes but the effects can be ameliorated by vaccines, and those vaccines have to be changed. But they reduce fatality and hospitalization and the need for people to stay home.

Dr. Krammer: In this scenario the virus is not going to disappear. It’s just going to stick around and become the fifth coronavirus that circulates in humans. The other four coronaviruses make up about 30 percent of all common colds, and they’re seasonal; they come in the winter like influenza.

Dr. García-Sastre: Some of these common coronaviruses that cause the common cold have been with us for a long time and are very different from SARS-CoV-2. They are happily living with us, rarely cause any major disease, and do not cause a threat.

Dr. Krammer: Now, influenza typically causes more damage than these common coronaviruses which are typically causing mild infection, except in people who have problems with their immune system who are sometimes brought to the intensive care unit. I think SARS-CoV-2 will land somewhere between influenza and human coronaviruses—between those two extremes.

Is it possible that this virus will simply disappear?

Dr. Palese: You can never exclude the possibility that this virus will peter out the way the coronavirus (SARS-CoV-1) did twenty years ago, when it emerged to cause some really high fatalities but disappeared. On the one hand it was a nightmare, but then it was over.

Dr. Krammer: I don’t think the virus will just disappear, but it might. We didn’t think there would be so many variants this quickly, especially not something like Omicron, so there might be surprises. I hope for society’s sake that this fades into the background and we’re not afraid every fall that another wave is coming. The scenario I would like to see in six months is that Peter and I – as virologists – are concerned about it but that the problem is insignificant enough so that the public does not have to be. We’ll see if that happens.

How do we continue to ensure protection from COVID-19?

Dr. Krammer: We have to look at the baseline immunity that exists in the population. If a lot of people have immunity and there is less virus circulating chances are that you either don’t get infected or, if you get infected, your immunity will be protect you against severe outcomes. Then the disease and infections become less relevant. And that is what we hope for. Now, you can get there through vaccinations—that’s the painless way, or you can get there by having had the infections, and that’s the painful way. But both contribute to having higher baseline immunity in the population. Unfortunately, even in this scenario, immunocompromised patients are still at risk of severe outcomes although there risk of getting infected is lower.

Dr. García-Sastre: Vaccinations are still the solution to the problem. We should make sure that as many people as possible are vaccinated and boosted.

Dr. Krammer: I think we need to keep working on vaccines against SARS-CoV-2. Right now we have this situation where the vaccine protects very well against severe disease if you’re not immune compromised. But those vaccines are not protecting very well from infection anymore. They did against the original virus, but not with the variants. That’s why, for example, we need a variant-specific vaccine for Omicron. There are ways to make vaccines differently so you get more sterilizing immunity, which would suppress infections more, in general, and that would make the world safer for those who don’t mount good immune responses.

Dr. Palese: In creating our COVID-19 vaccine at Mount Sinai, we are using the Newcastle-disease virus in a vector-driven approach. If the FDA [U.S. Food and Drug Administration] is agreeable and allows the comprehensive use of genetically modified viruses, such as ours, then we can prevent the emergence of these new variants by vaccinating right away with the correct vaccine against the new variant, and we should be in good shape.

Do you think the public needs a fourth vaccine right now?

Dr. Krammer: For populations that don’t mount optimal responses or their responses disappear quickly, there might be an advantage in getting another dose. But for the general population, I don’t think this is useful right now. If there is a fourth dose, it should be variant-specific, an adapted vaccine that reflects what’s circulating right now.

For immunocompromised individuals, there are already a couple of important therapeutic treatments—including PAXLOVID from Pfizer Inc., operating under the FDA’s emergency use authorization—that can help them to greatly reduce their risk of a severe outcome.

Is it feasible to create a universal coronavirus vaccine—similar to the universal influenza vaccine you are developing?

Dr. Krammer: By universal you mean a variant-proof SARS-CoV-2 vaccine, I assume? One that would protect against all variants? We’ve made a lot of progress with the universal influenza vaccine in the last few years. But vaccine development has just started for coronaviruses and there are a lot of approaches out there. Coronaviruses are very diverse. A truly universal coronavirus vaccine would include protection against SARS-CoV-1 and other viruses in that subgenus and then you have a bigger genus of betacoronaviruses and, in addition, you have alpha-, delta-, and gammacoronaviruses (meant are the coronavirus genera, not the SARS-CoV-2 variants). So developing a universal coronavirus vaccine that would protect against all of them is a very big ask. It might be possible at some point, but it is small steps now and would take a lot of time. Of course, something that protects against variants that are around now or could be developed within the next five years, that’s actually possible.

Milestone Gift From Marc and Jennifer Lipschultz Elevates Precision Immunology Research at Mount Sinai

Miriam Merad, MD, PhD

The Mount Sinai Health System has announced a transformative multimillion-dollar gift from Marc Lipschultz, who serves on Mount Sinai’s Boards of Trustees, and his wife, Jennifer, to the Precision Immunology Institute (PrIISM) at the Icahn School of Medicine at Mount Sinai.

PrIISM has undertaken an innovative and ambitious research agenda aimed at understanding the immune system’s universal role in human health, with the goal of combatting and preventing the world’s most devastating diseases. Marc and Jennifer Lipschultz’s generous support will strengthen PrIISM’s core research programs and the institute will be renamed the Marc and Jennifer Lipschultz Precision Immunology Institute in recognition of their investment.

Nearly every disease has an immune component, making PrIISM’s work particularly important. PrIISM is led by Director Miriam Merad, MD, PhD, a renowned physician-scientist and global leader in immunology, who also serves as Director of the Mount Sinai Human Immune Monitoring Center and Professor of Medicine (Hematology and Medical Oncology).

“We are so thankful to Marc and Jennifer Lipschultz for their visionary support of PrIISM,” says Dr. Merad.  “Their gift will allow us to expand our research and drive breakthroughs in immunology that will help us better understand and target the underlying foundations of major human disease.”

Under Dr. Merad’s leadership, PrIISM is already making pivotal advances in precision medicine and developing novel technologies to revolutionize the diagnosis and treatment of a broad spectrum of diseases, including cancer, neurodegeneration, atherosclerosis, and aging.

Brian Brown, PhD, Associate Director of PrIISM, leads the development of new cell and gene engineering approaches to understand and manipulate the immune system.

“The Lipschultz’s generous investment is extremely timely and will help us harness the extraordinary advances in our understanding of the human immune system to develop novel targets of diseases,” says Dr. Brown.

“Jennifer and I are proud to support the revolutionary immunology research at PrIISM,” says Mr. Lipschultz.  “We are excited to see how this meaningful work will transform the future of medicine and make a true difference in the lives of patients at Mount Sinai and beyond.”

Advancing Artificial Intelligence Through Philanthropy

David Windreich

Thanks to the outstanding generosity of the Windreich Family Foundation, the Icahn School of Medicine at Mount Sinai will advance its vision of integrating Artificial Intelligence (AI) and machine learning into research and clinical practice to amplify patient-centered care. This multi-million dollar gift will establish the Windreich Department of Artificial Intelligence and Human Health at Mount Sinai.

By establishing one of the first departments devoted to AI in a medical school, this gift represents Mount Sinai’s exceptional commitment to integrating AI throughout the Mount Sinai Health System. It will enable the recruitment of dedicated faculty, novel research initiatives, and the acquisition of any equipment and software that are mission critical to ensuring Mount Sinai continues to lead bold initiatives that embrace the power of technology to accelerate advances in both scientific research and clinical care.

Oversight of the newly named Windreich Department of Artificial Intelligence and Human Health will fall under the purview of its inaugural Chair, Thomas J. Fuchs, Dr.sc, who is also the Co-Director of the Hasso Plattner Institute for Digital Health at Mount Sinai. The new department was formed under the vision and guidance of Dennis S. Charney, MD, the Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine. “This gift will ensure Mount Sinai continues to be at the forefront of the AI-driven revolution of health care to the benefit of Mount Sinai’s diverse patient population,” says Dr. Charney.

“Our duty at the new department at Mount Sinai is to ensure that our patients are the main beneficiaries of the enormous impact AI will have on health care,” says Dr. Fuchs.  “To realize this vision, we are tremendously grateful for the gift from the Windreich Family Foundation. Mr. Windreich’s forward looking support will allow us to build a unique AI infrastructure at Mount Sinai and attract the world’s leading talent in this space.”

David Windreich, who serves on the Boards of Trustees at Mount Sinai, has a history of supporting AI and big data solutions in health care. His philanthropy extends to naming the Windreich Center for Bioinformatics at Mount Sinai. This Center is singularly focused on developing cutting-edge, web-based software tools and databases to facilitate the collection and analysis of diverse and complex data from human cells and tissues that will inform precise treatments for patients based on their unique genetic makeup. Mr. Windreich is also a former member of the Board of Directors for Sema4, a platform that uses machine learning and AI tools to analyze a database of more than 10 million patient genomic profiles and clinical records. Sema4 spun out of Mount Sinai in 2017 and went public at a $3 billion valuation in 2021.

“We have not yet reached the tipping point of how AI can play a major role in health care,” says Mr. Windreich. “My family is excited to play a role in supporting Mount Sinai’s initiative of being at the forefront of delivering technology solutions that will ultimately improve care and save lives.”

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