Four-Year $720,000 Grant will Enable Stern College’s Marina Holz to Investigate Breast Cancer Cell Growth

The American Cancer Society, the largest non-government, not-for-profit funding source of cancer research in the United States, has awarded Dr. Marina Holz, assistant professor of biology at Yeshiva University’s Stern College for Women, a $720,000 Research Scholar Grant. The four-year grant will be used to continue her work researching how the mTOR pathway affects the growth of estrogen-receptor positive breast cancer.

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With Faculty Support, Helen Unger Discovers Her Passion for Cancer Research at Stern; Wins Prestigious Award

Growing up in Cleveland, Ohio, Helen Unger watched her mother battle cancer and initially decided to join the fight by becoming a doctor.

Helen Unger chose Yeshiva University for its many research opportunities and supportive Torah environment.

Eager to roll up her sleeves and get to work, she graduated high school early and enrolled in pre-med studies at Yeshiva University’s Stern College for Women S. Daniel Abraham Honors Program—a plan Unger formed in ninth grade.

“I recognized that my situation in public school wasn’t ideal for me,” said Unger. She had recently become religious on her own and struggled to lead an Orthodox lifestyle in a secular world. Unger was anxious to launch her career in cutting-edge science and medicine, but she also longed to expand her understanding of religious Judaism and be part of an environment where its intricacies would be built into daily life.

“I knew I wanted to go to a college where being Jewish wasn’t something I just did on the side,” Unger said. When a little bit of research told her that YU had a high graduate and medical school acceptance rate, she knew she’d found the right place. “I knew that Stern would allow me to focus on excelling in Jewish studies and learning as well as the sciences.’ ”

As a freshman, Unger found her envisioned career path had evolved. Excited by the amount of research opportunities available to undergraduates on campus, she had started work in the breast cancer research laboratory of Dr. Marina Holz, assistant professor of biology. “In Dr. Holz’s laboratory, we work to identify therapeutic targets against which new cancer treatments can be developed,” said Unger. Holz’s problem-solving approach to cancer research fascinated her.

Unger and Holz, right, are working to identify therapeutic targets against which new cancer treatments can be developed.

“I fell in love with research,” Unger said. “I love how it allows scientists to innovate and design new and more effective therapies for disease without the pressure of following clinical protocols. I also like the fact that my work could develop therapies that will help a multitude of patients, not just one at a time.”

As a junior majoring in cellular and molecular biology, Unger was encouraged by Holz to apply for the Thomas J. Bardos Science Education Award for Undergraduate Students. She was recently selected as a winner and is the first YU student to be chosen. The two-year award, given to a handful of students across North America, is intended to inspire young science students to enter the field of cancer research. It provides them with unique educational opportunities in the development of their careers in science and a $1,500 stipend to attend the next two American Association of Cancer Research Annual Meetings, where Unger will have the chance to meet and hear from leading researchers and potentially present her research with Holz.

“I’m looking forward to the award putting me in touch with people who are higher up in the cancer research realm,” Unger said. “It provides me with good contacts and a lot of exposure to what’s going on in research around the world. I’m also excited to represent YU and Orthodox Jewry at the conferences and to show them what we’re all about.”

Unger with Anna Sedletcaia, a postdoctoral fellow in Holz's lab, who assists undergraduates with their research projects.

In addition, Unger recently co-authored an article with Holz and other students which has been published in the January 30, 2012 online edition of Oncogene, a high-impact research journal.

“Helen is a very successful student researcher who has contributed a lot to our work,” Holz said. She added that Unger’s award was an indicator not only of her personal achievement, but the caliber of the science students and faculty at Stern in general.

“Many of our faculty have active research programs which allow us to involve undergrads in our work,” said Holz. “We have real, relevant, nationally-acclaimed, nationally-funded programs and the latest biological and molecular techniques to employ in our labs. The fact Helen won this prestigious national award is a sign that we’re on the same level as any other major research university.” She added: “Helen is the first to win, but more will follow her.”

For Unger, relationships with faculty like Holz were enriching both academically and personally. “Dr. Holz has been a wonderful mentor,” she said. “The professors at Stern are there for you from everything, from your big questions about molecular biology to what kind of shoes you should wear to a conference. It’s like a little family.”

Unger also felt the warm, supportive atmosphere at Stern encouraged students to compete with themselves to do their best, rather than forcing rivalries with other students. “Stern is a small school and that means each student in my biology class is a person, not a number,” she said. “We all want to see each other succeed and get into top graduate schools and I think that’s the best environment for learning.”

Unger credits the warm, supportive atmosphere at Stern for bringing out the best in students.

Holz emphasized Stern’s collaborative approach to science. “When students do research here, they really have a home base,” she said. “They have a lab to come to between classes where they can hang out and get to know professors as they do research together, which allows them to form a personal mentorship with the faculty that leads to more career advancement opportunities and a better-rounded science education.”

This summer Unger will participate in the Sloan-Kettering Summer Undergraduate Research Program, an extremely selective program that gives students opportunities for hands-on research experience in cutting-edge biomedical research laboratories. Next, she hopes to pursue a doctorate at a New York City school—and possibly teach as well.

“I’d love to educate the next generation of scientists,” said Unger. “Biology is the study of life and there are so many things people don’t understand. I’d love to be a role model that could help students with that process.”

Einstein Receives $8 Million in Grants from NIH to Study How Cancer Spreads

The National Cancer Institute (NCI) has awarded Albert Einstein College of Medicine of Yeshiva University two grants totaling $8 million to study the microenvironments that drive the spread of cancer from the primary tumor to other parts of the body in the process known as metastasis.

“Although metastasis is responsible for the vast majority of cancer-related deaths, our understanding of this complex process is extremely limited and so are the opportunities for preventing metastatic disease,” said John Condeelis, Ph.D., professor and co-chair of anatomy and structural biology, co-director of the Gruss Lipper Biophotonics Center, director of the program in microenvironment and metastasis in the Albert Einstein Cancer Center, and holder of the Judith and Burton P. Resnick Chair in Translational Research at Einstein. Dr. Condeelis is a principal investigator on both grants.

The first grant, for $4 million over five years, will establish a tumor microenvironment research center (TMEN Center) at Einstein, one of 11 new national centers created by NCI’s Tumor Microenvironment Network. The Einstein center will be led by principal investigator Dr. Condeelis and co-principal investigator Vladislav Verkhusha, Ph.D., professor of anatomy and structural biology. Read full article at Einstein News…

Einstein Scientists Find Crucial Molecule Involved in Spread of Breast Cancer

Researchers at Albert Einstein College of Medicine of Yeshiva University have identified a key player in the spread of breast cancer. The findings, recently published in the online edition of Nature, identify a critical molecule that helps cancer spread beyond the primary tumor. The research highlights a potential new strategy against metastatic disease. The study’s senior author is Jeffrey Pollard, Ph.D., professor of developmental and molecular biology and of obstetrics & gynecology and women’s health at Einstein. He also holds the Louis Goldstein Swan Chair in Women’s Cancer Research and is the deputy director of the Albert Einstein Cancer Center.

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People rarely die from their primary (original) tumor. Instead, most cancer deaths occur because the cancer has spread, or metastasized, to other parts of the body. “By focusing on sites where cancer had spread, we were able to detect a molecule that stimulates metastasis,” said Dr. Pollard. “This raises the possibility that metastasis could be kept from progressing – or even prevented – if the stimulating molecule could be blocked. This we achieved in mouse models of breast cancer.”

Metastasis begins when cells break away from the primary tumor and gain the ability to move on their own. These cells invade nearby blood vessels (a process known as intravasation) and are carried by the bloodstream to other parts of the body. The bloodborne tumor cells then escape from vessels in a process known as extravasation. Once these tumor cells escape from the vessels, they seed new and deadly tumors that grow in these distant locations. Read full article at Einstein News…

American Association for Cancer Research Honors Einstein’s Susan Band Horowitz

The American Association for Cancer Research (AACR), the world’s largest organization dedicated to cancer research, has awarded Susan Band Horwitz, Ph.D., the Rose C. Falkenstein Professor of Cancer Research and co-chair of molecular pharmacology at Albert Einstein College of Medicine of Yeshiva University, its Eighth Award for Lifetime Achievement in Cancer Research.

Dr. Horwitz, who is also the associate director for experimental therapeutics at the Albert Einstein Cancer Center, is being honored for her pioneering research that established the mechanism of action of the cancer chemotherapeutic drug Taxol, also known as paclitaxel, which prompted the development of this drug as an important therapy for many common solid tumors.  Taxol has been used by more than one million patients worldwide to treat cancers of the ovary, breast and lung.

“Dr. Horwitz has had a direct impact on millions of cancer patients around the world through her work in understanding the mechanisms of action of paclitaxel and other cytotoxic drugs,” said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. “Her remarkable career and pivotal scientific contributions have influenced our understanding of how cancer drugs work and how to translate that knowledge into improved strategic treatments.”

“This award has great meaning for me because it results from a decision made by my peers,” said Dr. Horwitz. “This honor recognizes my laboratory and all of the students, fellows and visiting scientists, who have contributed so much to my research program.” Read full story here…

Sep 16, 2010 — On August 26, cancer researcher Matthew Levy, Ph.D., and his lab colleagues got some unusual visitors. Young actress Abigail Breslin and 13-year-old cancer survivor Pearce Quesenberry came to visit their research lab at the Albert Einstein College of Medicine of Yeshiva University as part of Stand Up To Cancer, a national effort to raise cancer awareness and fund research.

Dr. Levy is the recipient of a $700,000 Stand Up To Cancer grant that gives young, innovative scientists funding for high-risk, high reward research. He and his team are working on developing treatments that will attack cancer cells while leaving healthy cells alone, which could reduce or even eliminate the side effects of chemotherapy, which can range from mild to debilitating.

At the lab, the two teenage girls donned lab coats, peered through microscopes and got a look behind the scenes.

The Stand Up To Cancer telecast aired on Sept. 10 and raise funds that will accelerate innovative cancer research. The live, one-hour fundraising event was simulcast on ABC, CBS, FOX, NBC, Bio, Current TV, Discovery Health, E!, G4, HBO, HBO Latino, MLB Network, mun2, Showtime, Smithsonian Channel, The Style Network, TV One and VH1 and hosted by network news anchors Katie Couric, Diane Sawyer and Brian Williams.

The Stand Up To Cancer broadcast is dedicated to the 12 million U.S. cancer survivors, illustrating how groundbreaking research can change the tide in the fight against the disease.

The 2008 telecast helped raise over $100 million. To date, five multi-disciplinary “Dream Teams” of researchers from more than 50 institutions, as well as 13 young innovative scientists who are undertaking high-risk yet potentially high-reward projects have received SU2C funding.

For more information, visit www.su2c.org.

Dr. John S. Condeelis co-led the research team.

Dec 29, 2008 — In an important finding published online in “Developmental Cell,” researchers at Albert Einstein College of Medicine of Yeshiva University, along with collaborators at Massachusetts Institute of Technology, have identified a protein likely responsible for causing breast cancer to spread.

Metastatic cancer occurs when cancer cells from the original tumor travel to distant sites via the bloodstream. Most cancer deaths occur when cancer spreads to other organs. Trying to stop cancer before it metastasizes is the main goal of cancer treatments. A marker showing that cancer has spread would help doctors choose the best possible treatment options for patients. Upon diagnosis, 6 out of 10 breast cancer patients have cancer that is still in its primary location making the potential discovery of a marker for invasive cancer of tremendous value.

Early markers of metastatic breast cancer have been hard to find. In the Einstein-led study, researchers have identified a protein that is a promising candidate for a metastatic breast cancer marker.

The protein, called Menainv, is present in invasive cells within a breast tumor. These cells move into surrounding tissue and eventually to blood vessels. Menainv is not found in cells that stay within breast tumors, an indication that this protein contributes to the invasive and metastatic ability of tumor cells and is not just an ‘innocent bystander’.

The research was conducted under the direction of John S. Condeelis, PhD, professor and co-chair of anatomy and structural biology at Einstein and co-director of the Gruss Lipper Biophotonics Center and Frank B. Gertler, PhD, Ross Scholar Professor of Biology at MIT.

The latest research was aided considerably by the work of Jeffrey B. Wyckoff, principal associate of anatomy and structural biology at Einstein who, with Dr. Condeelis, developed the in vivo invasion assay used to isolate metastatic tumor cells from breast tumors thereby implicating Menainv as important for metastasis.

Evanthia T. Roussos, an MD-PhD student in Dr. Condeelis’ lab and primary co-author of the study, explains, “We have micro-needles filled with growth factors and tissue that we insert into a tumor on an anesthetized mouse. If a tumor cell is invasive, within four hours, it will crawl into the needles. We found that mouse breast tumor cells that we engineered to contain Menainv were invasive whereas cells that did not have Menainv were not.”

The study also found that tumor cells harboring Menainv are less likely to be responsive to newer breast cancer treatments that inhibit epidermal growth factor receptors (EGFR). Epidermal growth factor (EGF) has been shown to increase a breast cancer cell’s invasive potential. Drugs that inhibit EGF may lack effectiveness against tumor cells that express Menainv. That’s because Menainv cells are so sensitive to EGF that even the small amount of EGF signal that the drugs fail to block may be enough to stimulate EGF receptor and promote tumor cell migration and metastasis.

If Menainv behaves in humans the way it does in mice, researchers could develop an antibody test or PCR assay to identify it.

The current study builds on previous research by Dr. Condeelis’ group which identified Menainv as the isoform of Mena that is over-expressed in the invasive and metastatic subpopulation of tumor cells in breast tumors. The current study shows that Menainv forces tumor cells in mammary tumors of mice to become invasive and eventually metastasize to the lung.

The primary co-authors of the paper are Ulrike Philippar, MIT, Merck Research Laboratories and Evanthia Roussos, Albert Einstein College of Medicine, Department of Anatomy and Structural Biology; Gruss Lipper Biophotonics Center. Other authors include Matthew Oser, Yarong Wang and Jeffrey B. Wyckoff of Einstein; Sumanta Goswami of Einstein and Department of Biology, Yeshiva University; Hideki Yamaguchi, formerly of Einstein and now at Tokyo University of Pharmacy and Life Sciences; Hyung Do Kim and Douglas A. Lauffenburger, MIT; Silvia Giampieri, Cancer Research UK, London Research Institute; and Erik Sahai, Einstein and Cancer Research UK, London Research Institute.

Nov 25, 2008 — The American Cancer Society, the nation’s largest non-governmental funder of cancer research, has given its highest award, the Medal of Honor, to four Americans who have made outstanding contributions to the fight against cancer. Among the honorees is Susan Band Horwitz, Ph.D., distinguished professor and co-chair of the Department of Molecular Pharmacology at Albert Einstein College of Medicine of Yeshiva University, who is recognized for her groundbreaking research on the cancer drug Taxol (paclitaxel), which has been used by more than 1 million patients around the world to treat cancers of the ovary, breast and lung.

Other honorees include Senator Ted Kennedy, scientist Mina J. Bissell, Ph.D., and philanthropist Jon M. Huntsman. The awards were presented during an evening gala at the Waldorf-Astoria in New York City. What follows are excerpts from a conversation with Dr. Horwitz on her major contributions to cancer treatment.

“When I started working with Taxol in the 1970s, there was absolutely no indication that it would be useful in the clinic,” says Dr. Horwitz. “Of course I hoped, but I had no reason to think that it would turn into a drug that would help more than a million cancer patients.”

Bark from the Pacific Yew tree (Taxus brevifolia) was collected in 1962 by two botanists who were hired by the National Cancer Institute (NCI), a branch of the National Institutes of Health, to find natural products that might cure cancer. The isolation of Taxol from the bark by medicinal chemists at Research Triangle Institute was published in 1971.

Research into Taxol languished for years. The Yew tree was relatively rare and produced little of the compound. What’s more, isolating and extracting Taxol from the tree’’s bark was difficult. It wasn’’t until the mid-1970s that NCI researchers confirmed that Taxol had anti-tumor properties, but they couldn’’t figure out how it affected cells.

For that, they turned to Dr. Horwitz, a promising young researcher at Einstein who was known for her studies of naturally occurring small molecules and their use in cancer treatment.

Within months of receiving samples of the compound in 1976, Dr. Horwitz and her colleagues discovered Taxol’s mechanism of action. Some anti-cancer drugs kill cancer cells by wrecking the proteins needed to make microtubules, filament-like structures that play a crucial role in cell division.

But as Dr. Horwitz found, Taxol works in a completely different manner. Instead, the molecule sends cells into overdrive, churning out extra microtubules that clog up the cells’ innards. Taxol freezes the microtubules into bundles, preventing them from disassembling. As a result, cancer cells have no way to divide, and they soon collapse and die.

It was a stunning discovery, setting the stage for a whole new class of cancer chemotherapeutic drugs.

But first, Taxol had to be brought from the bench to the bedside, which was no easy task. Early clinical tests showed the drug to be quite toxic, delaying human trials for years. But Dr. Horwitz was undeterred. “We felt that this was a special drug, because it had a unique structure and mechanism of action,” she says.
Researchers at Einstein and other institutions eventually figured out how to transform the compound into a formulation that was safe for human use.

Finally, in 1992, 16 years after Dr. Horwitz first began studying the compound, the FDA approved Taxol for the treatment of ovarian cancer. Later, it was approved for use against advanced breast cancer and small-cell lung cancer. To date, Taxol is the best-selling cancer drug ever manufactured.

“I am very honored to receive this award from the American Cancer Society,” says Dr. Horwitz. “It is so important to realize that basic scientists can make significant contributions to clinical care.”

“I feel strongly that this is not my personal award,” she adds. “It is for my entire laboratory—for all the students, fellows, visiting scientists, and collaborators that have worked with me all these years.”

The story of Taxol is not over. Some tumors are resistant to chemotherapy, while others develop resistance over time, and Taxol is no exception. Dr. Horwitz is now working to pinpoint the molecular mechanisms that underlie Taxol resistance, in the hope of providing another powerful target for combating cancer.

She is also developing combination therapies, in which Taxol is given along with other chemotherapy drugs. The idea is to attack cancer cells from multiple angles, hampering their ability to develop resistance.

In addition, Dr. Horwitz is studying the molecular biology of microtubules for clues related to Taxol resistance. More specifically, she is examining whether the presence of different forms of tubulin (a building block of microtubules) might explain why some cancer cells are more responsive to Taxol than others.

One offshoot of this work may be the development of biomarkers that can be used to predict which patients will respond well to Taxol. “Taxol has side effects, and we don’t want to give the drug to people who are not going to get any benefit,” she explains.

Today, Dr. Horwitz is more optimistic than ever about curing cancer. “We’ve learned a tremendous amount in the 35 years since I got my first research grant, which was from the American Cancer Society,” she says. “I believe that with enough financial support, and with the brightest and the best young people going into cancer research, we should be able to overcome this disease.”

Dr. Margarita Vigodner was awarded a $300,000 grant for her research on the effects of second-hand smoke on male infertility.

Jun 26, 2008 — Yeshiva College and Stern College for Women professors will tackle male infertility, breast cancer, and supercritical fluids as recipients of three substantial science grants totaling close to half a million dollars.

Dr. Margarita Vigodner, assistant professor of biology at Stern College, was awarded a $300,000 Young Clinical Scientist Award by the Flight Attendant Medical Research Institute (FAMRI) for her research on the effects of second-hand smoke on male infertility.

Using laboratory mice as human surrogates and advanced cell analysis, Vigodner and two undergraduate students in the S. Daniel Abraham Honors Program at Stern will assess the changes in the animals’ testicular genes following their exposure to second-hand smoke. Her research is based on ten years of experience in the field of spermatogenesis (the development of sperm), male fertility, and reproduction health.

Male partners are responsible for infertility in at least half of all human couples, and for 39 percent of infertile men, their infertility is of an unknown cause or origin. Vigodner is working hard to identify its roots, and believes that “the problem of male infertility will be overcome in the foreseen future,” she said.

Dr. Marina Holz, assistant professor of biology at Stern, will study the role of the S6 Kinase 1 (S6K1) gene in breast cancer through a three-year, $75,000 grant from the Elias Genevieve and Georgianna Atol Charitable Trust.

After spending several years researching the molecular mechanisms of S6K1, Holz observed that the gene was over-expressed in cancers, especially breast cancer.

“I would like to identify specific targets of S6K1 in breast cancer that control cell proliferation and contribute to the cancerous phenotype,” said Holz. “The funds from this grant will help support acquisition of new equipment and reagents [chemical compounds] for the project.”

She will be working with Stern graduates Rachel Yamnik ’08S and Nilly Brodt ’08S, and current students Alla Digilova and Daphne Davis.

The American Chemical Society Petroleum Research Fund has awarded Dr. Bruce Hrnjez, associate professor of chemistry at Yeshiva College, $65,000 for his research on solvent effects in supercritical fluids. Yeshiva College will match $55,000 of that funding, for a total of $120,000 over three years.

Hrnjez’s work focuses on a molecule’s surroundings; the medium in which a molecule is dissolved can have an effect on the way the molecule vibrates, rotates, and interacts with light, and the way its chemical bonds break or form in a chemical reaction.

“Molecules are somewhat like people,” explained Hrnjez. “Environment affects behavior.”

Hrnjez, who has spearheaded the rebirth of experimental scientific research at Yeshiva College , created an experimental research laboratory in Belfer Hall on the Wilf Campus. His first paper to come out of this research appeared in 2005 in the Journal of Physical Chemistry, with student coauthors Samuel Sultan ’05Y, Georgiy Natanov ’07Y, David Kastner ’05Y, and Michael Rosman ’05Y.

For Hrnjez, the grant means more than just financial support for an important investigation. “It is external recognition from my peers that I have created a viable research program at Yeshiva College,” explained Hrnjez. “It is also external recognition of strong support from the Yeshiva administration.”