Announcing Multi-PI Planning Grants to Support Innovative Research
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.
Five teams of researchers from Columbia University Irving Medical Center 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.
The projects will investigate prospective genetic risk for Autism Spectrum Disorder; pathogenic drivers and actionable targets in Acute Myeloid Leukemia; intergenerational transmission of trauma; tumor cell microenvironment and prostate cancer progression; and learning health systems as a mechanism to improve the lives of patients with rare diseases. The awardees are:
Prospective Genetic Risk, Emergence, and Pre-Symptomatic Intervention for Autism Spectrum Disorder
• Wendy Chung, MD, PhD, Pediatrics - Clinical Genetics (Principal Investigator)
• Jeremy Veenstra-VanderWeele, MD, Psychiatry - Child and Adolescent (Co-Principal Investigator)
Given the recent advances in autism genetics, early detection and intervention could have a significant impact on outcomes in children diagnosed with autism spectrum disorder (ASD). Together with their collaborators, Drs. Chung and Veenstra-VanderWeele will leverage precision medicine to study individuals at genetic risk for ASD prospectively and the impact of pre-symptomatic genetic diagnosis. The team aims to build an Autism Center of Excellence that will identify genetically at-risk newborns, conduct longitudinal follow-up to detect early signs of ASD, and assess the impact on parental stress and decision making. The Planning Grant will enable the investigators to collect preliminary genomic data from the target infant cohort and engage their External Advisory Board in planning efforts for their P50 Autism Center of Excellence application.
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.
Center for Intergenerational Psychiatry
• Jonathan Posner, MD, Psychiatry - Child and Adolescent (Principal Investigator)
• Cristiane Duarte, PhD, MPH, Psychiatry - Child and Adolescent (Co-Principal Investigator)
Childhood adversity is a well-known risk factor for subsequent mental illness, and mounting preclinical research suggests that the effects of adversity may extend beyond the exposed individual to their children. Drs. Posner and Duarte and collaborators aim to study the intergenerational transmission of trauma and its effect on neurodevelopment and mental illness in the next generation. The researchers will explore the biological mechanisms of transmission and possible mechanisms for interventions to limit the impact on offspring brain and behavioral outcomes. This work will focus on the underserved communities that are disproportionally affected by adversities, underscoring the investigators’ commitment to health equity. The Planning Grant will allow the team to conduct preliminary genome and mRNA analyses and provide research and grant writing support for the team’s NIMH P50 application.
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.
Translating Rare Disease Discoveries into Improved Care via a Learning Health System
• Chunhua Weng, PhD, Biomedical Informatics (Principal Investigator)
• Paul Applebaum, MD, Psychiatry - Mental Health Service Research and Policy (Co-Principal Investigator)
• Wendy Chung, MD, PhD, Pediatrics - Clinical Genetics (Co-Principal Investigator)
• Cong Liu, PhD, Biomedical Informatics (Co-Principal Investigator)
Rare diseases affect 30 million Americans and cause significant morbidity and mortality. As clinical guidelines and treatments for rare diseases evolve rapidly, it is important to keep patients and providers abreast of the latest treatment and therapies. A Learning Health System (LHS), which generates knowledge, engages stakeholders, and implements behavior change to transform practice, could be critical to discover and apply knowledge for rare diseases to improve the care of rare disease patients. Drs. Liu, Chung, Applebaum, Weng and team aim to create an EHR-based rare disease LHS to translate the latest discoveries into timely diagnoses, effective management, improved health outcomes, and continuous learning for patients with rare diseases. The Planning Grant will support the team’s application for an NCATS Collaborative Innovation Award (U01), enabling the investigators to conduct stakeholder focus groups on ethical, legal, and regulatory issues; assess current data standards and workflows; and develop sharable software prototypes for clinical decision support and clinical trial recommendations.
See the list of all awarded team members and past Irving Multi-PI planning grant award recipients here