Division of Translational Medicine Research
Researchers in the Division of Translational Medicine are developing new treatments for cancer, chronic wounds, and osteoarthritis. We focus our investigative efforts on the following areas:
- promoting chondrocyte homeostasis in the treatment of osteoarthritis
- bone regeneration
- inflammation and immune-modulating drugs
- a novel biotherapeutic for the treatment of acute and chronic wounds
- hepatic cirrhosis and its therapy
- angiogenesis and atherosclerosis
- novel molecular targets for the treatment of cancer
- computational immunology research
- cardiovascular multiomics research
The Cronstein Laboratory, headed by Bruce N. Cronstein, MD, is focused on adenosine, a chemical that most cells and tissues release in response to stressors, such as hypoxia and inflammatory injury. In ongoing studies, the Cronstein Laboratory has demonstrated that adenosine, acting at its A2A receptors, is essential in maintaining chondrocyte homeostasis.
The researchers found that A2AR-deficient mice develop premature osteoarthritis. They also found that ecto-5'-nucleotidase deficiency in mice and humans leads to the development of osteoarthritis. Based on these findings, the researchers developed an intra-articular injection of liposomal preparations of adenosine and A2AR agonists, as well as a nanoparticle-bound adenosine. These novel agents are currently undergoing preclinical testing in preparation for therapeutic trials in osteoarthritis.
Bone Regeneration Research
The Cronstein Laboratory recently demonstrated that extracellular adenosine, acting at A2A and A2B receptors, promotes regeneration of bone and that the application of an agent, dipyridamole—which increases extracellular adenosine to three-dimensional printed scaffolds—dramatically improves bone regeneration at sites of critical bone defects. This approach is also useful for the repair of craniofacial abnormalities such as cleft palate.
Wound Healing Research
Leslie I. Gold, PhD, and her team discovered that the intracellular endoplasmic chaperone protein, calreticulin (CRT), enhanced the rate and quality of cutaneous wound healing in a porcine model—pigs heal in a similar way to humans—and a diabetic mouse model of experimental wound repair. Using human keratinocytes and fibroblasts in vitro, the laboratory showed that CRT induces migration and proliferation of keratinocytes to resurface the wound defect, and stimulates migration, proliferation, and induction of extracellular matrix proteins by fibroblasts.
In addition, CRT attracts macrophages into wounds and activates them to engulf bacteria and dead tissue for wound debridement. In addition to healing wounds by broad ranging and diverse effects, CRT heals wounds by a tissue regenerative process that includes epidermal appendage neogenesis and lack of scarring. These results are being translated from the bench to the clinic as a novel topical treatment of chronic wounds including diabetic foot ulcers, while the laboratory continues to investigate CRT’s mechanisms of action.
Cancer Biology Research
Dr. Gold and her team are also researching the loss of growth regulation in hormone-regulated cancers. The team was the first to show that TGF-β, estrogen, and progesterone regulate the protein levels of p27kip1, a cyclin-dependent kinase inhibitor, through the ubiquitin pathway, causing its degradation. The laboratory studies show that the degradation of p27kip1 is involved in the pathogenesis of endometrial cancer—an estrogen-induced cancer. The team has identified small molecule inhibitors of the E3 ligase complex Skp2–Cks1 that prevent estrogen-induced degradation of p27kip1, thereby increasing its levels to restore growth control. The Skp2–Cks1 inhibitors are being structurally optimized as novel therapeutics for different cancers that show rapid proliferation due to loss of nuclear p27 from high Skp2–Cks1 E3 ligase activity. The team is continuing to define molecular targets that it can translate into novel therapies for cancer prevention and treatment.
Cancer Proteogenomics Research
As part of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), Kelly V. Ruggles, PhD, and her team are applying computational and statistical methods to model biological systems and measuring the effect these have on human health. Dr. Ruggles is analyzing the proteomics, genomics, and transcriptomics of tumors to gain deeper insights about the static and dynamic status of cancer.
Computational Immunology Research
Dr. Ruggles’s laboratory is conducting research into human and mouse immunology in collaboration with the Division of Infectious Diseases and Immunology and the Department of Microbiology. The team is working on several projects using multiomic immunological profiling to gain a deeper understanding of immune activation and heterogeneity.
Cardiovascular Multiomics Research
Dr. Ruggles’s laboratory is part of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, supported by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH). As part of that collaboration, Dr. Ruggles and her team are developing novel methods that enable them to analyze multiomic data to characterize ischemic heart disease. The team’s goal is to understand the clinical manifestations of ischemic heart disease as well as the causes that drive its development.
The Division of Translational Medicine currently occupies 1,500 square feet of laboratory and office space within NYU Langone. We anticipate growing our footprint as more members join our team.
Translational Research in Progress (TRIP) seminars are sponsored by the Division of Translational Medicine, the Clinical and Translational Science Institute, and NYU Langone’s Department of Medicine. The seminars keep clinical researchers, basic scientists, and population health researchers abreast of ongoing research projects. They also stimulate collaborations among these scientists to promote translation of research advances from bench to bedside for patients.
TRIP seminars are open to researchers from NYU Langone and other NYU schools and colleges, and are conducted online. For more information about TRIP seminars or to find out how to be a presenter, please contact Shirley Cabrera, administrative coordinator, at email@example.com.
Grants and Funding
The team’s research is largely funded by grants from the NIH, as well as private foundations and the pharmaceutical industry.