The Albert Einstein College of Medicine is one of the nation’s premier centers for research, medical education and clinical investigation. Our faculty-inventors are well recognized in their respective fields and have found innovative approaches to addressing unmet medical needs. Our office works diligently to capture and promote these advances in medical research made at Einstein, so that they can be translated into clinical settings and benefit the public. If you are interested in learning more about any of the technologies or faculty-inventors below, contact our office.
Novel Targets for Lipid Regulation
Lipid droplets are distinct intracellular structures that are the primary storage medium for triglycerides and other fats. In addition to fats, the lipid droplets contain specific proteins that are believed to play a role in regulating their formation and size. These droplets allow the body to maintain energy balance at the cellular and whole-organism levels. However, during conditions where lipid droplet size or quantity increases to excess, such as in obesity, the risk for acquiring common debilitating diseases, such as Type 2 diabetes and cardiovascular diseases, increases.
Since little was known about the molecular mechanisms behind lipid droplet formation, Dr. Silver and his team have focused their research on finding the proteins and pathways that regulate their formation and stability in cells. Using gene-profiling techniques, they succeeded in identifying a set of novel RNA molecules, which they named "fat-inducing transcripts" (FIT). Further work on the proteins encoded by two of these transcripts, named FIT1 and FIT2, were found to be localized in the endoplasmic reticulum of the cell. The team performed experiments in liver cells and in mice that showed that introducing FIT genes into cells increased the amount of lipid droplets and triglycerides without increasing the overall levels of triglyceride biosynthesis. Dr. Silver’s team also performed a complementary experiment of silencing FIT RNA (using RNA interference technology), which resulted in the opposite effect of preventing lipid droplet and triglyceride accumulation in the cells. Thus, FIT RNA and protein may represent promising targets for a novel class of antiobesity and/or metabolism-modulating drugs.
The identification of these proteins provides the basis for establishing new animal models and drug-screening methods for the discovery and testing of compounds that can regulate lipid droplets in human tissues. Currently, Dr. Silver and his research team are doing further work that addresses the possibility that regulation of FIT1/FIT2 by drugs designed to target these factors can be a new avenue of potential treatment for obesity, diabetes and other syndromes.
Principal Investigator: David L. Silver, Ph.D.
Dr. David Silver joined the Einstein faculty as assistant professor in the department of biochemistry in 2005. He received his Ph.D. in genetics in 1996 from Michigan State University at East Lansing and completed a postdoctoral fellowship at Columbia University in the laboratory of Dr. Allan Tall in 2000. Prior to coming to Einstein, Dr. Silver was assistant professor in the department of medicine at Columbia, where he established a laboratory and research program focused on the identification and biochemistry of proteins involved in lipid and lipoprotein metabolism in the liver. Upon coming to Einstein, Dr. Silver continued work using the drug fenofibrate as a probe to examine novel lipid metabolic pathways, and to profile novel sets of genes involved in regulating these pathways. This work recently led to the discovery of the evolutionarily conserved FIT1 and FIT2 genes, which the Silver laboratory has shown to regulate lipid droplet formation (i.e., fat storage) in the cell. Through these and related projects in the laboratory, the goal is to gain a better understanding of the fundamental biochemistry of fat storage in the cells, particularly as it applies to the control of these pathways in diseases such as Type II diabetes, obesity and cardiovascular disorders. This research has begun to yield new targets for the potential development of novel drugs to treat these diseases.
Positron Emission Radiotherapy of Cancer
Often, when patients are diagnosed with cancerous tumors that are inoperable, they are prescribed a course of chemotherapy. Unfortunately, it is difficult to efficiently and effectively target the tumor without affecting surrounding tissues. Therefore, many clinicians are leaning toward positron therapy, which is a more targeted approach to selectively killing cancer cells. However, the current radiopharmaceutical agents available are limited, and therefore new agents with broader applicability are needed in order to reach all the patients in need. Positron Emission Tomography (PET) systems are used to track positron-emitting radionucleotides that are taken up by tumors. This is an established method for use in imaging and evaluating tumors in patients, which doctors use to detect and monitor the progression of the cancer.
One of the most widely used radiopharmaceutical reagents used in PET systems for diagnostic and imaging purposes is 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG). This radiolabeled compound has been used in over two million PET studies without any reported complications, showing that it is a safe compound to use in humans. Researchers at Albert Einstein College of Medicine have found that 18F-FDG can also have therapeutic benefits.
Preclinical studies suggest that 18F-FDG effectively kills breast cancer cells without significant marrow or parenchymal toxic effects. Furthermore, these studies show that positron therapy can inhibit tumor growth and increases survival rates. This has been shown in mouse breast cancer models.
Some advantages of this therapy include: (1) a higher precision at targeting tumors, which leads to less-negative effects on surrounding tissue; (2) a known compound that has little known toxic results; and (3) no changes observed in appetite and/or body weight, which alleviates known side effects.
Principal Investigator: Ekaterina Dadachova, Ph.D.
Dr. Ekaterina "Kate" Dadachova, a Sylvia and Robert Olnick Faculty Scholar in Cancer Research and associate professor of nuclear medicine and of microbiology and immunology, focuses her research on different applications of radioimmunotherapy, including infectious diseases; viral cancers by targeting viral antigens on cancer cells; and melanoma with antimelanin antibodies and peptides (all three projects in collaboration with Dr. A. Casadevall, Einstein). She is also investigating the therapeutic potential of 18F-FDG, a positron-emission tomography agent, for the treatment of metastatic cancers in patients (in collaboration with Dr. D. Paul, Lincoln Hospital, NY).
The technology of radioimmunotherapy of melanoma involves using radiolabeled monoclonal antibody to melanin to specifically target melanoma tumor sites and deliver a short burst of lethal radiation, without harming normal tissue. This technology was recently licensed to Pain Therapeutics, Inc., which has since then moved it into Phase I clinical trials.
Dr. Dadachova received her bachelor of chemistry degree in 1986 and her Ph.D. in physical chemistry in 1992 from Moscow State University. In 1993, she emigrated to Australia to begin postdoctoral work at the Australian Nuclear Science and Technology Organization (ANSTO), and in 1995, she was invited as a guest scholar to Oak Ridge National Laboratory (ORNL), where she worked in isotope production and radiolabeling of antibodies for cancer treatment. Upon returning to ANSTO from ORNL, she was promoted to Research Scientist. In 1998, Dr. Dadachova was invited to join the Radioimmune and Inorganic Chemistry Section of the National Cancer Institute (part of the NIH) as a visiting associate. In this position, she participated in all aspects of preclinical development and evaluation of radiopharmaceuticals, including radiolabeling, animal therapy and toxicity studies, until her recruitment to the Einstein faculty in 2000.
To date, Dr. Dadachova has published 82 peer-reviewed papers and is named inventor on 11 pending and/or issued patents. Ongoing research projects in her laboratory are funded by both NIH and industry grants. She currently serves on the editorial boards of Nuclear Medicine and Biology and Cancer Biotherapy and Radiopharmaceuticals.
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