However, these novel compounds need to be optimized, in terms of their properties and potency, to allow for testing in animals and ultimately in human clinical trials. Stockwell and collaborators have in prior research identified a specific R152H single amino acid alteration in the lipid repair enzyme, called GPX4 that is associated with a severe phenotype involving developmental issues, including a rare progressive disorder called Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) for which there is no cure. In laboratory studies, the researchers uncovered small molecules that can activate the variant, and potentially reverse its developmental damage in patients. AlQuraishi, PhD, assistant professor of systems biology.ĭr. Optimization of Small Molecules that Restore Enzyme Activity to R152H GPX4Ĭo-investigators: Farhad Forouhar, PhD, associate research scientist at the HICCC Mohammed N. This project could improve distribution of donated kidneys in a subset of donors with APOL1 variants, facilitate discovery of more precise treatment, and expand overall understanding of the role of APOL1 in chronic kidney disease at large. The team will incorporate precision donor-screening technologies, innovative immunologic studies, and state-of-the-art digital microscopy techniques to better understand the mechanisms of donor-transmitted APOL1-associated kidney diseases, an area ripe for research. Donor-transmitted APOL1-transmitted kidney diseases are still poorly understood. Black patients with kidney failure often receive kidneys from Black donors and therefore are more likely to receive kidneys with APOL1 variants that predispose them to early transplant failure.

Kidneys transplanted from Black donors have a shortened survival compared to white donors, which has been attributed to variants of the apolipoprotein L1 (APOL1) gene that is enriched in Black population.

The Immunopathology of Donor-Derived APOL1 NephropathyĬo-investigators: Kevin Gardner, MD, PhD, professor of pathology and cell biology Barry Freedman, MD, professor of medicine and chief of nephrology at Wake Forest School of Medicine Iuliana Ionita-Laza, PhD, professor of biostatistics The five projects are being led by principal investigators Ibrahim Batal, MD, associate professor of pathology and cell biology at Columbia University Vagelos College of Physicians and Surgeons (VP&S) Brent Stockwell, PhD, professor and chair of biological sciences at Columbia University Marie-Pierre St-Onge, PhD, associate professor of nutritional medicine (in Medicine and the Institute of Human Nutrition) at VP&S Raju Tomer, PhD, assistant professor of biological sciences at Columbia and Kelley Yan, MD, PhD, assistant professor of medicine and of genetics and development at VP&S. Jointly awarded by the Columbia Precision Medicine Initiative (CPMI), the Herbert Irving Comprehensive Cancer Center (HICCC), and the Irving Institute for Clinical and Translational Research (Irving Institute), the Precision Medicine Pilot Grants underscore Columbia University’s commitment to supporting diverse, cross-disciplinary research targeting the promise of precision medicine.Įach team will receive a one-year $100,000 grant to support their research. Recent progress is bringing us closer to earlier intervention and new therapeutic targets.Five research teams at Columbia University have been awarded a 2022 Precision Medicine Pilot Grant to advance the fields of cardiovascular disease, colorectal cancer, rare disease, organ transplant and precision psychiatry. Importantly, recent research building upon earlier findings of de novo recurrent CNVs at the 22q11.2 locus, has highlighted a de novo mutational paradigm as a major component of the genetic architecture of schizophrenia. Although the former had limited success, the role of rare genetic events, such as copy-number variants (CNVs) or rare point mutations, has become increasingly important in gene discovery for schizophrenia. More recently, the availability of powerful technologies, samples of sufficient sizes, and genome-wide panels of genetic markers facilitated systematic and agnostic scans throughout the genome for either common or rare disease risk variants of small or large effect size, respectively.

Early linkage and candidate association studies led to largely inconclusive results. Although a genetic component of schizophrenia has been acknowledged for a long time, the underlying architecture of the genetic risk remains a contentious issue.

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