Division of Nephrology
The Barasch Lab focuses on the mechanisms of kidney growth and kidney damage. Dr. Barasch’s work began with the identification of a method to generate fully segmented nephrons from renal progenitors (Cell, 1999) and because of this assay, Dr. Barasch has recently defined a novel and critical transcription factor in nephrogenesis and nephron patterning, a Cp2 like factor (JCI, 2014). During this search for growth factors he fourtuitously purified NGAL (Mol Cell, 2002); its expression demonstrated that the first response of the kidney to acute injury was production of an iron chelator for bacteriostasis (Nature Medicine, 2011) by a cell type (interacalated cells) that was not previously thought to play a role in acute kidney injury pathophysiology (JCI 2014). The work not only opened many doors for further inquiry in the response of the kidney to injury, but as a sequel, Barasch introduced the first biomarker of kidney damage to be used clinically (in Europe, Asia; JCI, 2005; Lancet, 2005; Annals of Internal Medicine, 2008; JACC, 2012). Dr. Barasch has been funded continuously by the NIH for the past two decades and is currently funded by two NIH RO1 grants and the March of Dimes. He is also co-Principal Investigator of an NIDDK-sponsored George O’Brien Urology Center (Multi-PI with Drs. Mendelsohn and Gharavi) studying the loss of urinary defense mechanisms as a result of genetic defects in urinary tract formation. He has been a member of the March of Dimes Study Section for 10 years and an ad-hoc reviewer at the NIH and Columbia’s CTSA. Dr. Barasch has hosted more than 30 college and medical, graduate and post-doctoral students in his lab; 7 are now independent scientists, 3 currently hold NIH funding. He also has a leadership role in developing educational programs and career tracks for aspiring clinician scientists. He is the Director of the PhD to MD program, Course Director of Molecular Mechanisms, and Director of the Clinician Scientist Track of House Staff Training in Internal Medicine. Dr. Barasch has received the Bomfalk and the Presidential Awards of Columbia University and recently the Provost Award in novel educational techniques.
The Gharavi Lab. Dr. Gharavi is a nephrologist with expertise in human genetics. His lab research is focused on the molecular genetics of kidney diseases, leading to the to the discovery of genes and loci for IgA nephropathy and congenital defects of the kidney and urinary tract. His lab also uses mouse models and cell based assays to study the biological mechanisms underlying kidney disorders. The Gharavi lab has recently demonstrated the utility of sequencing in the diagnosis and management of patients with nephropathy. Dr. Gharavi is extending this work to other adult constitutional disorders by leading a Center for Precision Medicine and Genomics. His ultimate goal is to bring personalized genomic medicine from the laboratory into patient care. To achieve this, the lab collaborates with investigators worldwide. In addition, the lab works with several national networks and consortia, including the CureGN study, the O’Brien Benign Urology Centers, the All of Us program. In the course of these research projects, Dr. Gharavi has trained a large number of students, post-doctoral fellows and young faculty members in careers in investigative medicine. He was named Mentor of the Year in 2018. For more information, please visit the Gharavi Lab Website and the CPMG website
The Honig Lab. Dr. Honig maintains both computational and experimental laboratories with about 20 post-doctoral fellows, graduate students, technicians and medical students. The guiding hypothesis of his work is that combining information about protein sequence and structure with biophysical analysis can reveal how biological specificity is encoded on protein structures. The emphasis of the computational group is on fundamental theoretical research, the development of software tools, and applications to problems of biological importance. The function of the experimental group ranges from biophysics, biochemistry, x-ray crystallography and bioinformatics to studying the structure and function of proteins, nucleic acids, and membranes. Combined, these separate strategies have successfully explained many biological phenomena. For example, through a combination of biophysical studies and molecular simulations, Dr. Honig’s group revealed how adhesion receptors such as cadherins are designed by evolution to have precisely defined homophilic and heterophilic differential binding affinities that in turn determine cell sorting behavior. A crucial experimental discovery was the demonstration that adherens junctions, cell-cell junctions whose formation is mediated by the dimerization of cadherins located on apposed cells, are formed via a two-dimensional phase transition, involving trans (apposed cell) and cis (same cell) interactions. The biological roles of these specific binding mechanisms currently are being investigated in the kidney in vivo in collaboration with Dr. Sampogna. Dr. Honig is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. He is recipient of the Founders Award of the Biophysical Society, the Alexander Hollaender Award in Biophysics from National Academy of Sciences, Christian B. Anfinsen Award from the Protein Society, and DeLano Award for Computational Biosciences from the American Society for Biochemistry and Molecular Biology, and is a Fellow of the American Association for the Advancement of Science and of the Biophysical Society. Dr. Honig receives funding through a R35 (NIGMS), NSF (MCB), a U54 grant from the NCI and the Gates Foundation. Notably, Dr. Honig has an outstanding track record for mentoring over 100 young scientists over the past 30 years, and many have become leaders in the field. For more information, please visit the Honig Lab Website.
The Kiryluk Lab conducts research on the genetics of complex phenotypes with primary focus on immune-mediated kidney disease and other forms of primary nephropathy. This group has completed large genome-wide association studies for IgA nephropathy involving over 20,000 individuals across multiple international case-control cohorts (Nat Gen 2011 and 2014). These studies identified multiple susceptibility loci and provided novel insights into the disease pathogenesis. They also demonstrated that the cumulative frequency of risk alleles closely parallels the variation in IgA nephropathy prevalence across continents, suggesting that genetic risk may in part explain disparities in disease prevalence among Asian, European and African populations (PLoS Gen 2012). Moreover, this group has described strong genetic contribution to the process of defective O-glycosylation of IgA1, demonstrating that serum levels of galactose-deficient IgA1 have high heritability in family-based studies of children with IgA and Henoch-Schönlein nephritis. These findings gave rise to an original multi-hit pathogenesis model of IgA nephropathy that describes sequential steps and molecular candidates involved in the disease development (JASN 2011, JCI 2014). The ongoing efforts of the Kiryluk Lab aim to refine this model and to dissect the precise pathogenic mechanisms underlying genetic susceptibility to nephropathy using systems genetics approaches. Other active projects include: GWAS and sequencing studies for membranous nephropathy, genetic studies of kidney transplantation outcomes, genetic predictors of primary disease recurrence in kidney allografts, and polygenic prediction of kidney disease, its progression, and complications. The lab participates in several national research networks, including the CureGN Study (UM1 funded by the NIDDK), eMERGE-III Network (U01 funded by the NHGRI), iGeneTRAiN network (U01 funded by the NIAID), Kidney Precision Medicine Project (UH3 funded by the NIDDK), and the Global COVID-19 Host Genetics Initiative network. For more information, please visit the Kiryluk Lab Website.
The Landry Lab. Dr. Landry is the Hamilton Southworth Professor of Medicine and the Chair of the Department of Medicine. He has established the Division of Experimental Therapeutics at Columbia where he investigates intractable health challenges, such as drug addiction (Science 1993, JACS 2001; JACS 2002), heart failure (PNAS 2008, PNAS 2005, Science 2004), and treatments for Huntington’s disease (Bioorg Med Chem Lett 2009), Alzheimer’s disease (Biochem Pharmacol 2020), and malaria (ACS Chem Biol 2015) using small molecules. His clinical research and clinical practice centers on his discovery that vasopressin insufficiency contributes to vasodilatory shock and can be treated by vasopressin infusions (NEJM 2001, 2008; Sci American, 2004). This insight has resulted in the worldwide use of vasopressin as a non-toxic therapy for septic shock. For these insights, he was elected to membership on the President’s Council on Bioethics (2008-2009) and he received the Presidential Citizen’s Medal, one of our nation’s highest honors. In 2016 Dr. Landry was inducted into the New Jersey Inventors Hall of Fame, acknowledging his patented innovative scientific contributions to medicine, ranging from cancer research to cardiovascular biology. He is a ubiquitous presence at Columbia who has mentored hundreds of students and faculty alike, establishing with Dr. Barasch the PhD to MD program and the Clinician Scientist Track of Housestaff Training. As a practicing clinician-scientist, nephrologist and intensivist, as a world-class organic chemist, and as Chief of Medicine, Dr. Landry is a unique and irreplaceable resource. He is the director of The Organic Chemistry Collaborative Center (OCCC), which specializes in organic synthesis, probe development, drug discovery, and pharmacokinetic studies, and has facilitated and greatly accelerated the translation of bench research to pre-clinical and clinical trials for a number of projects. The OCCC has received funding from federal and state government grants, industrial grants, and Columbia-sponsored grants, e.g., NIH (PPG, U01, R01, R21, and S01) and DoD grants. In the past, it also served as the chemistry core for the NIH-sponsored Columbia University Molecular Libraries Screening Center and the NYStem-sponsored Columbia NYSTEM High-Throughput Screening and Chemistry Shared Core Facility. Publications, patents, and, as of October 2021, 7 startups have emerged as a result of the research performed at the OCCC. For more information, please visit the center’s website.
The Sampogna Lab. Dr. Rosemary Sampogna is an Associate Professor of Medicine at Columbia University. Her research is focused on the molecular and genetic mechanisms that specify kidney architecture and ultimately determine function. She developed a 3-dimensional map that outlines the trajectory of kidney development throughout gestation. When applied to organs that developed under conditions of malnutrition or in the setting of growth factor mutation, this normative map provided an essential link between kidney architecture and the fundamental morphogenetic mechanisms that guide development. This map also identified the presence of a molecular timer that coordinates repetitive morphogenetic events that shape the kidney by regulating precise exchange of molecular signals between separate primordial tissue compartments. Another project is underway in collaboration with Drs. Barry Honig and Larry Shapiro to investigate the role of cadherins during kidney development. Cadherins comprise a set of receptors that mediate cell-cell interactions via specific binding and are expressed in well-defined patterns during nephrogenesis. Our groups have integrated biophysical binding and specificity predictions with mouse models in which cadherin expression in the kidney was altered systematically. This project aims to rationally design modified cadherins in vivo that will affect morphogenetic processes in highly predictable ways.
The Sanna-Cherchi Lab. Dr. Sanna-Cherchi’s main area of research involves the genetics of rare forms of kidney diseases and their complications. During the past 12 years his lab established a network of investigators across more than 20 countries worldwide recruiting patients for genetic studies, focusing on congenital anomalies of the kidney and urinary tract and primary causes of nephrotic syndrome. His work spans the entire spectrum of genomics research. To complement his sequencing approaches for human traits, he has developed new mouse models for congenital defects of the urinary tract. In a very creative approach, he is using zebrafish modeling to dissect genes within structural variants associated with developmental defects. His data integrating exomes, CNVs and zebrafish modeling suggest that one can successfully address complex genomic disorders using systematic, multidisciplinary approaches. In particular, his work provided a strong genetic link between pediatric kidney diseases and neurodevelopmental phenotypes, including autism, intellectual disability, schizophrenia, and others, with important repercussions beyond the field of nephrology. His work on congenital kidney defects and pediatric renal diseases has been published in prestigious journals, including NEJM (2013), JCI (2015), AJHG (2007, 2012, 2015), JASN (2005, 2009, 2014), and KI (2011, 2015) and many others. Dr. Sanna-Cherchi has had independent funding since 2009 (American Society of Nephrology, American Heart Association, as well as NIH R21 and R01 awards). Most recently he was selected as a Paul Marks scholar, one of the most prestigious young investigator awards at Columbia University. He also has a successful track record for securing funding for his trainees (American Association of University Women, AAUW Fellowship; KNAW Ter Muelen Grant; Italian Society of Nephrology Fellowship).