YU Professor Dr. Holz Receives Two NIH Grants to Research Cancers and Rare Diseases

By: Ailin Elyasi  |  November 16, 2017

In early August, The Doris and Ira Kurkin Professor of Biology at Stern College for Women, Dr. Marina Holz, was awarded two major NIH research grants to continue her work investigating Lymphangioleiomyomatosis (LAM)  and Triple-Negative Breast Cancer (TNBC) treatments.

Dr. Holz focuses her research on rare and little understood diseases. For instance, LAM affects 2,000 women in the US, which leaves this disease often overlooked in the scientific community. LAM cells are abnormal tumor cells which metastasize to the lungs, kidneys, lymph nodes, blood vessels, and lymphatics and typically affect women of childbearing age. By devoting her research to LAM and other little researched disorders, Dr. Holz increases the quality of life for the women who feel overlooked by research. In the three-year clinical trial that begins this fall, Dr. Holz, along with the University of Cincinnati, will be experimenting  with different drug combinations to eliminate LAM cells. The $712,442 grant funding that the National Institute of Health’s (NIH) Heart, Lung, and Blood Institute allocated to Dr. Holz’s lab will sustain the project. The clinical trials will take place at the University of Cincinnati.

Based on pre-clinical trials, Dr. Holz demonstrated that two drugs, sirolimus and resveratrol, can in combination be effective in bringing women with LAM into remission. Currently, the Food and Drug Administration has approved sirolimus as the treatment course for LAM. Dr. Holz demonstrated that with resveratrol, a naturally occurring chemical found in the skin of grapes used to make red wine, Sirolimus could be all the more effective in treating LAM.

“I am thrilled that this grant will allow us to rapidly build upon the basic and preclinical studies that started in my lab in 2014 and led to a synergistic collaboration with our clinical partners at University of Cincinnati, and our industry partner Evolva, the provider of resveratrol,” says Holz. “This grant will allow us to make substantial progress towards validating new therapeutic options for treatment of LAM, and will serve as a model of cross-disciplinary collaboration and rapid implementation of future clinical trials.”

Dr. Holz also received a $501,000 grant again from the NIH to research estrogen receptor alpha’s role in TNBC. A metastatic and aggressive cancer, TNBC most affects younger people, African Americans, Hispanics, and individuals with the BRCA1 mutation.

The difficulty in treatment of TNBC rests on the fact that it lacks the usual receptors targeted by successful breast cancer treatments, leaving only aggressive chemotherapy as a treatment option. However, Dr. Holz believes that focusing her efforts on the TNBC’s noteworthy overexpression of estrogen-related receptor alpha can best illuminate better treatment methods for TNBC.

“The wealth of the generated knowledge will allow us to establish a long-term research project to identify putative cellular targets to be studied in greater detail with the goal of exploring new avenues in breast cancer research, and develop new interventions and prognostic markers of therapy response,” said Holz. “Expanding the use of tamoxifen and rapamycin, both safe and FDA-approved drugs, may clinically benefit millions of women suffering from TNBC, with the potential to reduce disease mortality.”

Dr. Holz’s interest in her work is based on two main reasons. “The scientific reason is that LAM and many types are breast cancer cells carry mutations that cause abnormal activity of Mechanistic Target of Rapamycin (mTOR), a protein that has been of interest to our lab for a long time. mTOR regulates the growth and proliferation of cells, and when abnormally active, it can cause formation of tumors.” The scientific protein link connects the research of LAM and TNBC.

Michal Auerbach, a 2017 SCW graduate and a research assistant in Dr. Holz’s lab, explains the significance of mTOR, saying “[the mTOR] pathway is the most important pathway you’ve never heard of. It’s important for regulating the cell cycle, and synthesizes multitudes of signals, such as energy levels, cellular stress, and nutritional intake. It is this aspect that makes these diseases so hard to cure: we cannot cut out these signals altogether because we need them to live, but at the same time we have to find a way to control this type of overexpression in diseased cells”

But Dr. Holz also mentions a second reason–the personal incentive that researching treatments for breast cancer and LAM provides her, saying “both breast cancer and LAM are primarily diseases of women, which gives us a sense of mission.”

Indeed, everyone working at her lab agrees with the positive work setting she has established for SCW students and graduates, providing scientific opportunities for women. Commenting on her experience at Dr. Holz’s lab, Michal Auerbach states “I’ve been working [at Dr. Holz’s lab] since June, along with another recent graduate from Stern, Amanda Rubin. We’ve both enjoyed our experience in the lab. The reason I chose to work here is because I wanted a positive working experience, and the Holz Lab is one that fosters questioning and understanding in a supportive environment.”