Stavroula Kousteni, Emmanuelle Passegué, and Michael Shen among 5 teams of researchers who have been awarded Irving Institute Multi-PI Planning Grants

April 15, 2021

The Irving Institute for Clinical and Translational Research, in conjunction with the Columbia University Clinical Trials Office and the Herbert Irving Comprehensive Cancer Center (HICCC), announces the winners of the 2021 Irving Multi-PI Planning Grants

CSCI Members Stavroula Kousteni, Emmanuelle Passegué, and Michael Shen are among five teams of researchers from Columbia University Irving Medical Center who have been awarded Multi-PI Planning Grants to support the submission of multi-component biomedical research grants (e.g., SPORE, U54, P01, P50) and large multi-PI research grants (e.g., NCATS U01, MPI grants that require NIH preapproval). These one-year awards will allow the teams to build out their NIH applications to pursue innovative research across a wide range of conditions and diseases.

 

Epigenetic Remodeling, Emergency Myelopoiesis and Stromal Cell Signaling-induced Stem Cell Reprograming in AML Transformation

Stavroula Kousteni, PhD, Physiology – Research (Principal Investigator)

Emmanuel Passegue, PhD, Genetics and Development (Co-Principal Investigator)

Adolfo Ferrando, MD, Pediatrics (Co-Principal Investigator)

Acute Myeloid Leukemia (AML) is a cancer of the blood and bone marrow that affects some 20,000 people each year in the U.S. While newer targeted therapies have been introduced in recent years to treat AML, the prognosis of the disease remains poor. 

Dr. Kousteni and collaborators will perform a comprehensive analysis of mechanisms that converge on pre-cancerous hematopoietic stem cells (HSC) in order to better understand disease progression in AML. This analysis involves genetic and epigenetic changes acquired in HSCs or triggered by cells in their bone marrow microenvironment and amplified by cell dynamics changes that occur under aging-related stress. The team will apply targeted and genome-wide single-cell genomics, epigenomics, state-of-the-art animal models, and genetic CRISPR editing technologies to identify and validate pathogenic drivers and actionable targets involved in AML contributing to tumor progression and resistance to therapy.

 

Investigating Cell-intrinsic and Extrinsic Interactions in Prostate Cancer at the Single-cell Level

Michael Shen, PhD, Medicine - Hematology and Oncology (Principal Investigator)

Cory Abate-Shen, PhD, Molecular Pharmacology and Therapeutics (Co-Principal Investigator)

Despite recent breakthroughs in prostate cancer research and treatment, castration-resistant prostate cancer continues to pose a serious health issue. Following androgen deprivation therapy (ADT), a common treatment for prostate cancer, prostate tumors frequently recur in a castration-resistant form, which is more aggressive and difficult to treat.

To understand the mechanisms that drive prostate cancer progression to advanced disease, Drs. Shen and Abate-Shen will investigate the interplay between tumor cells and their surrounding stromal and immune microenvironment in promoting prostate cancer progression, metastasis, and treatment-resistance. Their multi-project approach incorporates expertise from colleagues at Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine. Their work will elucidate key events associated with advanced prostate cancer, such as neuroendocrine differentiation, when prostate tumor cells turn into neuroendocrine cells that are highly resistant to ADT, and metastasis, when prostate tumor cells spread to the bone and other organ sites.

 

Read more about their research