An anonymous $100 million contribution to Einstein, announced in 2023, has already begun to transform biomedical investigations and educational programs at the College of Medicine. 

“Our scientists do an exceptional job of securing federal and foundation grants for their research, which traditionally covers salary and lab expenses for their projects,” explains Yaron Tomer, M.D., the Marilyn and Stanley M. Katz Dean at Einstein and chief academic officer at Montefiore Einstein. “But to maintain a successful, robust research ecosystem, you need philanthropy.”

The recent donation is providing support across the full research spectrum—from bolstering the work of graduate students and early-career investigators to advancing discoveries made in the lab into clinical practice. 

“This inspirational gift ensures our position as a biomedical and educational powerhouse,” continues Dr. Tomer. “In addition, it has had a ripple effect of inspiring other donors to support us and help drive forward Einstein’s research and educational missions.”

Here, we describe four initiatives made possible through the transformational $100 million gift. That amount includes two separate Einstein 2030 Innovation Funds totaling $15 million, which provide support for scientists to initiate research and help translate those discoveries into therapies.

GPS has proved to be a godsend for drivers venturing from point A to point B. Researchers trying to steer discoveries from the laboratory bench to the ultimate destination—drugs approved  to treat disease—need navigation help as well. Now there is a GPS for Einstein researchers: the Einstein 2030 Acceleration Fund. 

This new support mechanism enables researchers to generate data needed to advance their biomedical discoveries through the drug-development pipeline. “The Acceleration Fund will go a long way toward increasing the value and appeal of discoveries to biopharmaceutical companies or venture capital investors for further financing, licensing, or purchase in order to bring them to clinical trials,” says Dr. Tomer. 

The Acceleration Fund plans to award from four to six one-year grants annually through 2030, offering up to $350,000 to each recipient. “When we evaluate applicants for these grants, we’re asking such questions as: Will the drug address an unmet medical need? Will it be a first- or best-in-class therapeutic? Would it change the standard of care? What are competitors doing in the field?” says Janis Paradiso, director of Einstein’s office of biotechnology and business development. “But first and foremost, we’re looking for strong science.”

Therapeutic Antibodies for Blood Cancers

Amit Verma, M.B.B.S., interim chair of oncology, associate director for translational science at the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center (MECCC), and co-director of MECCC’s Blood Cancer Institute,  is among the first class of recipients of the accelerator funding. He is using his grant to develop antibodies for treating the blood cancer myelodysplastic syndrome (MDS) and, potentially, the associated disease acute myeloid leukemia (AML). 

His project focuses on two proteins, S100A8 and S100A9, that contribute to the growth and spread of blood cancers by suppressing the immune system. The proteins also create a pro-inflammatory environment and can cause anemia, which can lead to crippling fatigue in MDS patients. But no one has figured out how to inhibit them. Dr. Verma and colleagues, including Rongbao Zhao, Ph.D., research associate professor of oncology and of medicine at Einstein, may have found a solution.

By working with animal models and developing new biochemical assays, they have identified a set of antibodies that can target and neutralize the S100A8 and S100A9 proteins. When tested on the diseased blood-forming stem cells, the antibodies increased the ability of those stem cells to produce healthy red cells—a promising start. 

“But these are animal-derived antibodies that won’t work in patients, because the human immune system would reject them,” notes Dr. Verma, who is also a professor of oncology, of medicine, and of developmental & molecular biology and the Susan Resnick Fisher Chair in Brain Cancer Research at Einstein. 

“We might have been able to attract investors to support this work, but that can be challenging at this early stage,” says Dr. Verma. 

Pressing on the Accelerator Pedal

That’s where the 2030 Acceleration Fund comes into play. Using his grant, Dr. Verma has already begun creating “humanized” antibodies, meaning changing the molecular backbones of the animal antibodies so that they resemble those in humans. Once they are tested in tissue culture and the researchers secure a series of clearances from the U.S. Food and Drug Administration (FDA), the antibodies can be evaluated in patients with MDS. Such trials could be broadened if the antibodies show promise against other diseases in which the proteins are thought to play a role, including AML and inflammatory bowel disease.

Meanwhile, Einstein has received a provisional patent for Dr. Verma’s animal-specific antibodies. In addition, Dr. Verma and his colleagues have launched a biotechnology startup, Roshon Therapeutics, to help them develop the antibodies, obtain FDA clearances, and rapidly enter clinical trials.

“If all goes well, I think we can get the antibodies into clinical trials in two years,” says Dr. Verma. “We want to push this forward as quickly as possible, which we couldn’t do without help from the Einstein Acceleration Fund.”

Before receiving grants from the National Institutes of Health (NIH), early- and mid-career investigators must usually generate preliminary data showing that their proposed projects are feasible—a hurdle that can prevent promising research from advancing. Now, as part of the anonymous donor’s gift, the Einstein 2030 Seed Fund will support researchers’ efforts to generate the critical data and proof-of-concept studies needed to secure NIH grants. 

Starting this year and continuing through 2030, the Einstein 2030 Seed Fund will annually distribute $700,000 to support faculty members engaged in “basic science research with potential translational applications.” Individual awards range from $50,000 to $150,000. 

One of 2024’s eight recipients is Stephanie Rudolph, Ph.D., assistant professor in the Dominick P. Purpura Department of Neuroscience and of psychiatry and behavioral sciences at Einstein, who is conducting innovative research into the origins of Alzheimer’s disease.

Most research on Alzheimer’s disease focuses on its middle or late stages, when memory loss, confusion, and changes in personality become apparent. But pathological changes in the brain probably start many years earlier. “Currently we can’t identify those early predictors of Alzheimer’s,” says Dr. Rudolph. “And treating the more-advanced stages has proven extremely difficult.”

Dr. Rudolph and her lab will use her seed funding to further pursue the genesis of Alzheimer’s, with the goal of nipping it in the bud. “Prevention is the ultimate goal,” she says. “Rather than trying to slow Alzheimer’s after it has already progressed, we have some promising and novel hypotheses for preventing its initiation.”

The lab is building on the work of Dr. Rudolph’s former collaborator Evan Macosko, M.D., Ph.D., a physician investigator at Harvard Medical School. He discovered that a population of nerve cells near the surface of the brain dies in early Alzheimer’s. Dr. Rudolph wants to determine why those neurons die and if their loss triggers a chain of events that make the disease advance.

Using mouse models and other techniques, Dr. Rudolph’s team is testing two hypotheses. The first is that cerebrospinal fluid, the watery substance surrounding the brain and spinal cord, ferries neuron-killing molecules to the brain. “We think such neurotoxic molecules might result from inflammation, metabolic dysfunction, or preexisting mood disorders that are known to increase the risk for an Alzheimer’s diagnosis later in life,” says Dr. Rudolph. The research is a collaboration with Simone Sidoli, Ph.D., assistant professor of biochemistry at Einstein, who will help determine which molecules in cerebrospinal fluid may lead to Alzheimer’s.

The second hypothesis is that the death of those surface neurons causes the widespread damage to neurons that is the hallmark of Alzheimer’s disease. “We plan to genetically target those surface neurons in mice to eliminate them or sever their connections to other neurons downstream,” Dr. Rudolph says. “Then we’ll examine both the brain tissue and the behavior of mice, looking for signs of Alzheimer’s pathology.”

If her hypotheses prove correct, scientists may finally have biomarkers for identifying Alzheimer’s in its earliest stages and find ways to protect those crucial nerve cells, she says. “I’m excited by the idea that one day we may be able to delay or even prevent this devastating disease. The seed funding will allow my students and me to acquire the materials, mouse lines, and reagents to test our key hypotheses, which we otherwise wouldn’t have the resources to do,” Dr. Rudolph says. “I’m extremely grateful that someone was willing to trust a young investigator like me to pursue a high-risk, high-reward concept.” 

In addition to enabling  some new Ph.D. students to enroll at Einstein each year, the anonymous gift also provides “bridge funding” so that a number of graduate students can launch or continue promising research projects. 

One of this year’s bridge grant recipients is Rita Yazejian, a fourth-year Ph.D. candidate, whose studies of a mouse model of brain cancer may lead to strategies to treat its recurrence in children. “The work that I am doing now with mice is too preliminary to get specific funding from the National Institutes of Health, but it has a lot of potential,” she explains. 

The anonymous gift will provide Ms. Yazejian with a $45,000 grant to continue her research with Allison M. Martin, M.D., assistant professor of pediatrics and of microbiology & immunology at Einstein and director of the pediatric neuro-oncology program at the Children’s Hospital at Montefiore (CHAM).

When I came to Einstein, I wanted to do research in cancer that could be moved into the clinic sooner rather than later,” Ms. Yazejian says. “I find it important to connect my basic science and my research to the bigger picture—why we’re doing this and why it matters.”

She and her colleagues are studying a rare type of brain cancer called medulloblastoma, which primarily affects school-age children. When this cancer relapses, it becomes notoriously resistant to attack by immune cells and doesn’t respond well to chemotherapy or radiation. “We want to help kids with relapsed medulloblastoma who don’t really have any treatment options left, so our lab focuses on novel ways to manipulate the immune response against tumors,” she says.

Ms. Yazejian is studying the PI3K signaling pathway, which is activated in medulloblastoma and other human cancers. She hypothesizes that inhibiting the PI3K pathway in medulloblastoma cells will dampen their ability to prevent the immune system’s T cells from multiplying—and, ideally, enable T cells to clear medulloblastoma tumors. 

In recent experiments, Ms. Yazejian treated mouse medulloblastoma cells with a PI3K inhibitor for 48 hours and then co-cultured the treated cells with mouse T cells for five days. The results, described in June 2024 in the journal Neuro-Oncology, have been promising: Measurements of T-cell levels showed that medulloblastoma cells treated with the PI3K inhibitor were less successful in suppressing T-cell proliferation than untreated medulloblastoma cells co-cultured with T cells.

Her mentor, Dr. Martin, says the bridge grant “will allow Rita’s experiments to evolve beyond their original framework so that we may apply for additional NIH grants to continue in this research area.” Ms. Yazejian already won a poster award at CHAM’s Pediatric Research Day, and she presented her findings in June at the International Symposium on Pediatric Neuro-Oncology in Philadelphia. 

Ms. Yazejian worked at the NIH before coming to Einstein and then rotated into three Einstein labs before finding a home in Dr. Martin’s. “There is a lot of cancer in my family,” she says. “Working in a translational lab to develop potential new cancer therapies is very important to me.”

Carpenters are only as good as their tools, the old saying goes. The same could be said for biomedical researchers. Thanks to the anonymous gift, the College of Medicine has accelerated its investments in the latest tools and technologies that foster the translation of ideas into discoveries. With $17.5 million, Einstein is revitalizing its Shared Scientific Facilities and Cores, which offer a wide range of cutting-edge analytic, engineering, and production services focused on work with proteins, genes, cells, and tissues. 

The Shared Scientific Facilities and Cores support the efforts of hundreds of investigators around the Einstein campus, including Carolina Rodriguez-Tirado, Ph.D., a postdoctoral fellow in microbiology and immunology. 

“A cancer diagnosis is hard enough, but hearing that it has spread is very scary,” says Dr. Rodriguez-Tirado, who came to Einstein in 2022. “It means that cancer cells may already be colonizing other organs even before a diagnosis is made. For new patients, this is one emotional shock on top of another.”

A native of Santiago, Chile, Dr. Rodriguez-Tirado specializes in cancer dormancy, studying how cancer cells escape a primary tumor and hibernate in distant body parts, only to awaken years or even decades later to seed new metastatic tumors. What regulates the biology of these disseminated cancer cells (DCCs) is poorly understood—and hugely important. By and large, primary tumors aren’t fatal, but metastatic tumors are.

Dr. Rodriguez-Tirado—in collaboration with her mentor, Maria Soledad Sosa, Ph.D., associate professor of microbiology & immunology and of oncology—is looking for molecules that regulate dormancy, using mouse models of cancer. Her ultimate goals are to identify biomarkers that can predict which patients are at high risk of metastatic disease and to develop therapies that maintain dormancy in DCCs or promote their eradication, thereby extending the period of metastatic-free disease and, presumably, survival.

To carry out these studies, Dr. Rodriguez-Tirado analyzes slices of tumors from mice, looking at levels of protein expression within tumor cells. From these analyses, she can determine what genes control dormancy and metastasis and what signaling pathways they affect. “These analyses used to take six months for each experiment. With the Analytical Imaging Facility’s new Hamamatsu NanoZoomer S60 slide scanner, we can do that same analysis in two weeks,” says the researcher.

Dr. Sosa’s and Dr. Rodriguez-Tirado’s studies have found that NR2F1, a transcription factor (a molecule that regulates gene expression), plays a major role in controlling the dissemination of cancer cells during the early stages of tumor progression and in maintaining the dormancy of DCCs. The researchers have since identified a molecule that can induce NR2F1 activity and block the capacity of malignant cancer cells to exit dormancy, helping move scientists one step closer to a therapy that prevents relapses. “Our findings are a proof of principle that it’s possible to limit metastatic growth by activating dormancy mechanisms,” Dr. Sosa says.

The Analytical Imaging Facility provides a comprehensive array of light and electron-microscope imaging services to the Einstein community. “Our new Hamamatsu NanoZoomer S60 slide scanner allows researchers to determine how DCCs infiltrate different tissues, what regulates the dissemination, and how these cells are reactivated to form new metastases,” says Vera DesMarais, Ph.D., research professor of cell biology and director of light microscopy in the Analytical Imaging Facility. 

“Another new tool, the Leica THUNDER microscope, allows us to study the organization and regulation of DNA replication and genomic instability, which has implications in research areas such as aging, neurodegenerative diseases, and cancer,” she adds. “The new microscope will support studies of the role of intracellular calcium fluxes in cardiovascular and metabolic disorders.”