Over the last two decades, gifts from Evelyn Gruss Lipper, M.D. ’71, to Albert Einstein College of Medicine have helped make it a leader in using advanced imaging to study how complex diseases get started and progress in the human body.

Now Dr. Lipper’s family philanthropy, the EGL Charitable Foundation, has made a major new gift to create Einstein’s Integrated Imaging Program for Cancer Research (IIPCR). The gift will help Einstein and Montefiore Einstein Cancer Center (MECC) investigators translate their laboratory research findings into clinical tools for diagnosing and treating life-threatening metastatic cancers (in which tumor cells have spread beyond the primary tumor).

“Dr. Lipper’s visionary generosity provides a path for bringing basic science advances to bear on intractable disease,” says Gordon F. Tomaselli, M.D., the Marilyn and Stanley M. Katz Dean at Einstein and executive vice president and chief academic officer at Montefiore Medicine. “With her support, patients will benefit from speeding promising discoveries into effective treatments, with the goal of improving cancer care for our Montefiore-Einstein patients.”

The Making of a Philanthropist

Dr. Lipper has been interested in science since her sophomore year in high school. “It was an exciting time, with the flowering of genetics and other scientific advances,” she recalls. “I wanted a career in medicine, and my parents didn’t discourage me.”

The fact that few women went into medicine at that time was no deterrent, and she found a welcoming home at Einstein, where a fifth of the Class of 1971 was female—an unusually large percentage in that era. “Einstein has always been socially progressive,” says Dr. Lipper, an honorary member of the Board of Trustees.

Like her classmates, Dr. Lipper spent countless hours learning her craft in hospitals and clinics serving the city’s most disadvantaged citizens, offering a perspective on healthcare that shaped her long career in pediatrics at Weill Cornell Medicine. Philanthropy came later, after raising four daughters, conducting clinical research, and practicing medicine. “I really didn’t focus on philanthropy until I retired,” says Dr. Lipper.

Using her parents as role models, she taught herself the art of charitable giving. “I didn’t have any formal training in philanthropy,” she says. “I am able to take a hands-on approach and identify meaningful projects to invest it. I also look for novel ideas that would benefit from an active sponsor.”

Observation is Critical

When Dr. Lipper decided to support research at her alma mater, she focused on imaging, a decision influenced by her own professional experience, as well as her interest in the use of new technology to improve health outcomes. “In science, observation is critical to understanding,” she says. “I took up that theme and went with it.”

Dr. Lipper’s initial gift to Einstein, in 2000, was instrumental in establishing the Gruss Magnetic Resonance Research Center (MRRC) under the leadership of Craig Branch, Ph.D., director, and Michael Lipton, M.D., Ph.D., associate director. Einstein scientists could now use MRI—a noninvasive imaging tool involving powerful magnets and radio waves—to open a window into metabolism, structure, and function.

It soon became clear that recent advances in the field of biophotonics could complement and expand upon MRI findings by attaining much higher resolution than was possible with MRI alone. Biophotonics uses photons (light particles) to examine and manipulate living systems, producing insights at the molecular level into cell function in health and disease. Biophotonics’ potential as an imaging tool inspired Dr. Lipper to make a second major gift to Einstein, establishing the Gruss Lipper Biophotonics Center (GLBC) in 2006, co-directed by Robert Singer, Ph.D., and John Condeelis, Ph.D. The GLBC has been co-directed since 2022 by Julio Aguirre-Ghiso, Ph.D., David Entenberg, Ph.D., and Vladislav Verkhusha, Ph.D.

Working separately, scientists in the two Gruss imaging facilities have achieved important advances:

• Using an advanced MRI-based technique called diffusion tensor imaging, Dr. Lipton showed that repeatedly heading a soccer ball increases the risk for brain injury and cognitive impairment.
• Dr. Singer invented a new type of imaging, called super registration microscopy, which allowed for unprecedented resolution in living cells. The team was able to illuminate something never before seen: individual mRNA molecules (which carry the instructions for making proteins) passing through the nuclear envelope on their way to the cytoplasm.
• Drs. Condeelis and Entenberg have developed several novel microscope technologies for use in intravital imaging. One such technology, infrared multiphoton imaging, allows researchers to observe the behavior and fates of individual cells in living animals.

Creating the Integrated Imaging Program (IIP)

The success of the GLBC research served to catalyze collaborations between researchers in the MRRC and in the GLBC. “To take this work to the next level, we really needed to combine MRI with multiphoton optical imaging—which would require a substantial investment in equipment and personnel,” says Dr. Condeelis, the Judith and Burton P. Resnick Chair in Translational Research, professor of cell biology and of surgery, scientific director of the Analytic Imaging Facility, and chair emeritus of anatomy and structural biology. In 2012, responding to this need, the EGL Charitable Foundation provided funds to establish Einstein’s IIP, co-directed by Drs. Condeelis, Singer and Branch.

The IIP has spurred numerous advances over the years. For example, IIP researchers have:

• Directly visualized how memory-associated messenger RNA in living neurons respond to neuronal activity in real time, potentially revealing how memories form and providing insight into neurodegeneration, stroke, and mental illness;
• Created a high-resolution imaging method for detecting whether two molecules are physically interacting or come close to each other merely due to chance, which could reveal dysfunctional RNA-protein interactions responsible for genetic disorders including neurodevelopmental and neurodegenerative diseases and cancer.
• Discovered how tumor microenvironment of metastasis (TMEM) “doorways” in blood-vessel walls allow cancer cells to spread from primary breast tumors to other parts of the body.

The TMEM doorway discovery caught the eye of none other than Francis Collins, M.D., Ph.D., then director of the National Institutes of Health (NIH). In 2016, he showcased Dr. Condeelis’ video of metastasizing cancer cells on his official blog. IIP multiphoton intravital images also graced the walls of the Obama White House and inspired new technology funding for NIH’s Cancer Moonshot program.

Ripples in a Pond

Every dollar of the EGL Charitable Foundation gift for the IIP has attracted another five dollars in extramural research funding says Dr. Condeelis. Some of those dollars helped fund a series of innovative clinical trials showing that the TMEM doorway score can accurately predict whether tumors in breast cancer patients are likely to metastasize. These clinical trials also provided important new insight into the mechanism by which tumor cells disseminate and how ethnic diversity can contribute to differences in clinical outcome in patients.

Dr. Lipper’s gifts have also influenced education.Thanks to the IIP’ssuccess in devising new technologies for diagnosing and treating cancer, Einstein won a major NIH T32 training grant enabling third-year surgery residents to conduct translational cancer research for two years.

Bench to Bedside

The IIP achieved its original purpose: catalyzing collaborations between researchers in the MRRC and in the GLBC. By the end of 2021, it became clear that something else was needed: a way to move the basic-science discoveries into the clinic.

“Ultimately, the goal of biomedical research is to improve human health,” said Dr. Condeelis. “And in our case, we are focused on developing new diagnostics, prognostics, and therapies and getting them to patients quickly so we can help physicians better identify and treat cancer. The only way to do this is to further develop our promising findings and efficiently move them into clinical trials.”

 This is already happening. For example, the IIP revealed how tumor cells disseminate during metastasis—findings now poised to guide targeted drug development and clinical applications for several types of cancer in addition to breast cancer. But a more formal support system needs to be put in place to build and reinforce this bridge from the laboratory bench to the wards.

The EGL Charitable Foundation stepped in once again, providing funds to create Einstein’s Integrated Imaging Program for Cancer Research (IIPCR), which will open in 2023 under the direction of Dr. Condeelis. This latest gift will expand Einstein’s research portfolio to include lung and pancreatic cancers and involve investigators from fields including radiology, oncology, surgery, pathology, veterinary medicine, and epidemiology.

The new gift will also provide vital support for young physician-scientists, giving them protected time to conduct translational research, acquire preliminary data for grant applications, and obtain independent research funding. Leading the breast, pancreas, and lung cancer programs, respectively, will be three Montefiore Einstein Cancer Center (MECC) physician-scientists: Maja Oktay, M.D., Ph.D., a pathologist who studies tumor progression and metastasis and racial disparities in cancer and co-director of the Tumor Microenvironment and Metastasis Program at MECC; John McAuliffe, M.D., Ph.D., a surgeon with expertise in pancreatic cancer and TMEM doorway biology; and Brendon Stiles, M.D., a surgeon who specializes in lung cancer and the problem of immune privilege in cancer treatment and MECC associate director of surgical oncology.

Bridging the Valley of Death

The IIPCR’s TMEM doorway prognostics and companion diagnostics studies are now in a challenging stage of development known in the scientific community as the “Valley of Death.” The NIH, the country’s major underwriter of biomedical research, generously supports the front and back ends of the research continuum—basic research and clinical trials, respectively. Yet, it doesn’t fund the time-consuming and costly middle stages of research, where investigators attempt to turn discoveries into testable drugs and technologies. Although the pharmaceutical and biotechnology industries sometimes fund this work, many promising discoveries never make it over the valley.

[Dr. Lipper] is a shining example of how the combined efforts of our research and philanthropic communities can address major healthcare challenges and ultimately improve the health of our community.

John Condeelis, Ph.D.

“That’s the beauty of this latest EGL Charitable Foundation gift to fund the IIPCR,” says Dr. Condeelis. “For the next 10 years, it will provide us with new resources to bridge the valley of death and bring more discoveries to clinical use. More specifically, we will be able to focus on developing, identifying, and validating drugs that target tumor cell dissemination, on completing pre-clinical testing, and on moving into pilot patient trials in collaboration with pharmaceutical industry partners.”

Improving Patient Care

By funding the IIPCR, the EGL Charitable Foundation will boost the further development of imaging innovations so they can reach the patients who need them. A prime candidate is the TMEM Activity-MRI test developed by Drs. Branch, Condeelis, and George Karagiannis, D.V.M., Ph.D. This noninvasive, prognostic, and diagnostic test is poised for use in the clinic. By using MRI to measure the number of TMEM doorways in a breast cancer patient’s primary tumor, the test can predict the risk of the cancer’s spread to other parts of the body and also evaluate a patient’s response to therapy. The test has been validated in retrospective clinical trials and in a recent prospective pilot study described last September in Nature pj-Breast Cancer.

With IIPC’s support, researchers hope that the TMEM Activity-MRI test will improve clinical care by helping physicians:

• Recognize patients at high-risk for metastasis, leading to better treatment strategies
• Prescribe medicines that help “close” TMEM doorways, preventing cancer from spreading
• Monitor, in real time, the risk that chemotherapy may be creating more pro-metastatic doorways, and suspending treatment in response

The EGL Charitable Foundation’s new gift also includes seed funding vital for the IIPCR’s Therapeutics Development Program, which will be led by Steve Almo, Ph.D., professor and chair of biochemistry, the Wollowick Family Foundation Chair in Immunology, and co-director of the MECC Cancer Therapeutics Program. This funding will make it much more likely that the Therapeutics Development Program’s new drugs and innovative tests in the IIPCR will successfully cross the “Valley of Death” that has doomed so many other early-stage discoveries.

Importantly, the foundation’s gift will enable cancer trials initiated in the IIPCR to be expanded into regional trials to improve diagnostic and treatment strategies. These trials, involving five collaborating partner cancer centers in New York City, will be organized by the New York Pathology Oncology Group led by Dr. Oktay.

“Dr. Lipper’s extraordinary vision, persistence, and generosity is an inspiration to all of us in the translational research community,” says Dr. Condeelis. “She’s a shining example of how the combined efforts of our research and philanthropic communities can address major healthcare challenges and ultimately improve the health of our community.”

Lessons Learned

“Perhaps the most important lesson I’ve learned as a philanthropist is that it’s not simply a matter of giving money away,” says Dr. Lipper. “You want to give it effectively and make an impact. What could be better than advancing medical technologies that improve people’s health?” Today, she could teach a master class on the subject.