Basic Science Labs


The Al-Awqati Lab. A central research theme of the Al-Awqati lab is the characterization of stem cells in the adult kidney. The kidney is able to regenerate after injury. Because stem cells divide very slowly, genetic methods were used to identify label-retaining cells in the kidney, diagnostic of stem cells. His group subsequently localized the stem cell niche to the papailla and has characterized the response of these cells to ischemia. In addition, his lab has identified the regulation of the response of the collecting duct to acidosis. This work produced a new paradigm for regulation of trans-epithelial transport later found in other ion transporters. Two types of intercalated cells (IC) were identified—the alpha-IC that secretes acid and the beta-IC, with reverse cell polarity, that secretes HCO3-. The secretory characteristics of these cells can inter-convert to accommodate changes in acid-base status. Dr. Al-Awqati is the recipient of numerous awards in recognition of his research including the NIH MERIT Award, the Columbia Triennial Award in Science, the Robert W. Berliner Prize of the American Physiological Society, and the Homer W. Smith Award of the American Society of Nephrology. He has served as an editor of Science, The Journal of Cell Biology, The Journal of Clinical Investigation, and Kidney International, and is a member of the editorial boards of many other journals. For the past three decades he has been a leader in the field of nephrology and investigated basic scientific problems with broad clinical implications. He has mentored numerous post-doctoral trainees who today hold important leadership positions in academic 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 focuses on human genetics research in nephropathy and congenital kidney defects. The lab applies state of the art genomics approaches to resolve the pathogenesis of these traits and through this work has identified many genes and loci predisposing to these disorders. This work has increasingly broader implications in Precision Medicine research, and he the lab is now also studying the optimal indications for genomic technologies for the diagnosis and targeted care of patients with chronic kidney disease. Ali Gharavi is Professor of Medicine and Chief of the Division of Nephrology. He is also the Director of the Columbia Precision Medicine Program for Kidney and Liver Diseases. In the past decade, Dr. Gharavi has developed a world-class program studying the genetics of complex kidney traits. He collaborates with many basic and clinical investigators worldwide and has a successful track record of organizing multidisciplinary groups for research and educational purposes. In the course of these research projects, he has trained a large number of students, post-doctoral fellows and young faculty members in careers in investigative medicine. His trainees have received funding from the American Heart Association, the American Society of Nephrology, the International Society of Nephrology, or the Telethon Institute. Dr. Gharavi was the recipient of the Ewig Clinical Educational Award at Columbia University, awarded to individual faculty members for their outstanding contributions to teaching. He also received the New York State award in Personalized Nephrology, which in part, provides support for training of junior faculty members. Dr. Gharavi is also co-Principal Investigator of an NIDDK-sponsored George O’Brien Urology Center (Multi-PI with Drs. Mendelsohn and Barasch) aiming to apply a multidisciplinary approach to study the genetic basis of urinary tract defects. For more information, please visit the Gharavi Lab Website.

The Honig Lab. Dr. Honig maintains both computational and experimental laboratories with over 20 post-doctoral fellows, graduate students, technicians and medical students. The guiding hypothesis of his work is that combining information about protein sequence 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 study the structure and function of proteins, nucleic acids, and membranes. Combined, these separate strategies have successfully used computational approaches to explain biological phenomena. Through a combination of biophysical studies, statistical mechanical theory and multi-scale 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 biologic 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, and is a Howard Hughes Medical Institute Investigator. 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. In addition to funding from HHMI, Dr. Honig receives funding through R01 (NIH), NSF (MCB), and two U54 grants. 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 kidney phenotypes with primary focus on glomerulonephritis and other forms of primary nephropathy. This group has recently completed two 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. This research is funded by the National Institute of Health, the American Society of Nephrology, the New York State Translational Research Program, and the Columbia CTSA Precision Medicine Program. The lab also participates in several national research networks, including the CureGN Study (UM1 funded by the NIDDK) and the eMERGE-III Network (U01 funded by the NHGRI). For more information, please visit the Kiryluk Lab Website

The Landry Lab. Dr. Landry is the Samuel Bard 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), Huntington’s and Alzheimer’s proteins (Eur J Med Chem 2013) and Malaria (ACS Chem Biol 2015) by the invention of novel small molecule inhibitors. 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. Dr. Landry 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 provides Organic synthesis, ADME studies and high-throughput screening to search for therapeutic compounds, and can greatly accelerate translation of bench research to pre-clinical and clinical trials.

The Sampogna Lab. Rosemary Sampogna is the Assistant 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).


 
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