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Adjunct Faculty, BiologyLander College of Arts and Sciences

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Dr. Barasch has made many contributions to science, including:

(A). Generation of Epithelia and Tubules and the Identification of a Critical Transcription Factor. I identified a set of factors that converted mesenchyme into epithelia. Mesenchymal clusters (isolated from rat embryos) were treated with conditioned media from UB cells and conversion activity was followed until single proteins were purified, such as LIF and eventually its family members, (Crlf-Cardiotrophin). While knockouts unfortunately had limited phenotypes, a ~40% reduction in mass, our finding made it possible to synchronously generate epithelia and consequently identify a conversion transcriptome, including 78 transcription factors. Subsequently, I cloned each factor and found one induced tubulogenesis in 100% of isolated rat mesenchyme. We generated a conditional deletion of this factor, Tfcp2L1, in mice and found that many cell types were missing from the kidney and, most intriguingly, the intercalated cell failed to develop. ChIP demonstrated the Cp2 like target genes which proved to be the structural genes of the distal tubule and collecting ducts as well as regulators of Notch signaling. In sum, this work identified a novel transcription factor that regulates patterning.                 

(B). Identification of a Clinical Biomarkers of Kidney Damage. One of the growth factors identified in our epithelial screens in (A), was called Lipocalin 2 (NGAL). Working with P. Devarajan, we found that NGAL was dramatically upregulated in the kidney by stimuli associated with acute injury. In >630 patients in a single center and >1630 patients in an international study, I found that NGAL: (i) was upregulated 10-1000 fold in dose-response with the intensity of the damaging signal; (ii) was not upregulated by simple volume depletion, hence distinguishing true-tubular damage “intrinsic AKI” from prerenal-azotemia; (iii) was expressed within 3 hours due to intrinsic promoter characteristics (NGAL is a “ready to go gene”); and (iv) was reversibly expressed. NGAL was approved by the FDA and by the Ministry of Health, Japan and Korea and by European Medicine Agency for human use. Our study in Pondicherry India and in New York demonstrated that a NGAL dipstick can predict AKI.

We turned to mice, rats, dogs, and pigs and found that: (i) NGAL RNA was expressed by the TALH and IC and PC within three hours of injury; (ii) using in situ, my reporter mouse (NGAL-Luciferase) construct, and isolated RNA directly from the TALH and collecting ducts by LCM and TU-RNA pulldowns to document NGAL expression, NGAL was synthesized only in the zone of damage; and (iii) urinary NGAL (uNGAL) was derived from the kidney as determined by comparing the kinetics of kidney lcn2 message with uNGAL, infusing Alexa-NGAL or NGAL:Ent:55Fe, all of which were prevented from reaching the urine by megalin. If we mutated dozens of surface amino acids, NGAL passed through the nephron into the urine excreting iron providing a novel type of iron chelator. Finally cross-transplanting KO kidney into wt lcn2+ mice and vice versa demonstrated that the kidney was the origin of urine NGAL in the absence of liver damage. Thus, non-creatinine characteristics and non-canonical localization taught us unexpected pathways relevant to urogenital illness such as UTI and AKI.          

(C). The Collecting Duct and Bladder Defend the Urinary System. We found that cloned NGAL was red because NGAL had interacted with a bacterial molecule known as the siderophore Ent: (i) NGAL blocked the growth of bacteria due to sequestration of siderophores, but mutant NGAL which failed to bind siderophores had no effect; (ii) Lcn2-/- and Tfcp2l1-/- mice could not clear a UTI; (iii) UTI’s stimulate duct cells to secrete NGAL and to acidify the urine, all of which limit bacterial growth; (iv) the deletion of intercalated cells by knocking out the novel Tfcp2L1 transcription factor resulted in poor clearance of bacteria; (v) urinary bacteria bind directly to intercalated cells and activate TLR4; and (vi) NGAL not only bound bacterial siderophores, but mammalian “simple catechols” which, like bacterial siderophores, bound and sequestered iron. (vii) In addition to NGAL the bladder expresses heme transport and metabolic pathways and novel heme sensors to detect UTI induced hematuria. Together, these findings bring together iron biology, urinary infection, and kidney damage. 

(D). Non-Transferrin Bound Iron (NTBI) Supplies Iron; Iron Deficiency Causes Chronic Kidney Disease To test whether NTBI was active in embryogenesis, we created TfR1f/f. We found that (i) nephrogenesis was possible without TfR1 in global and chimeric kidneys composed of TfR1 ko and wt type cells; (ii) a novel receptor for ferritin called Scara5 was expressed by capsule and cells surrounding the ureter, accounting for localized ferritin capture; and (iii) postnatal kidney development required TfR1; TfR1 KO resulted in cystic degeneration after birth but essentially normal kidneys throughout gestation. Given that TfR1 knockout cells cannot utilize transferrin, NTBI was proven to be a physiological entity that provided adequate amounts of iron before birth but that Tf deficiency is a new cause of postnatal cystic CKD. Exogenous supply of iron reversed cystogenesis.

(E). Training the Next Generation in Molecular Mechanisms Presidential Award and two “Provost Awards” in novel educational techniques to create (i) an education in biochemical and molecular biology underlying Medicine, a course called Molecular Mechanisms and (ii) a pathway for aspiring clinician scientists in Residency (iii) I am one of the directors of OBrien Center Summer Program (iv). mPI of NYC-KUHR Training Grant.

Education

  • BA, Biochemistry, Dartmouth College
  • PhD, Cell Biology, Columbia University College of Physicians and Surgeons
  • MD, Columbia University College of Physicians and Surgeons

Honors and Awards

  • 2023, FDA Approval, NGAL predicts kidney injury.,     
  • 2018, Ewig Clinical Scholar Award
  • 2017, The March of Dimes Study Section—the Committee S
  • 2007-12, Irving Fellow of Columbia University
  • 2012, Presidential Teaching Award of Columbia University.
  • 2010, Charles W. Bohmfalk Award for Teaching in the Clinical Years
  • 2008, American Association of Physicians
  • 2007-16, March of Dimes Study Section
  • 2005, Garvey Scholar and Member of the Glenda Garvey Teaching Academy
  • 2005, Salt and Water Club
  • 2003, The Doctor Harold and Golden Lamport Research Award
  • 2002-7, Fellow of the Irma T. Hirschl/Monique Weill Foundation 
  • 2002, AstraZenecaYoung Investigator Award of the American Physiological Society
  • 2000, American Society for Clinical Investigation
  • 1995/6, Zambetti Assistant Professor of Medicine
  • 1988, Public Health Ambulatory Care Award; The Louis Gibofsky Memorial Prize
  • 1988, Association of Anatomy Chairs, “Parafollicular Cells, Serotonergic Neural Crest Cells 
  • 1988, Dr. Alfred Steiner Award for Medical Research; Associated Medical Schools Awards 
  • 1980, BA, Magna cum Laude, High Distinction Biochemistry; Citation: Italian Renaissance Art

Publications

  • Verbitsky M, Khosla P, Bivona D, et. al. "Urobiota analysis and genome-wide association study in pediatric recurrent urinary tract infections and vesicoureteral reflux." JCI insight, 11(2), (2025) . pii: e199689. doi: 10.1172/jci.insight.199689
  • Gopal TS, Xu K, Muller Y, et. al. "Prospective Study of a Point-of-Care Diagnostic Test for Acute Kidney Injury in a South Asian Hospital." Kidney international reports, 10(6), (2025) 1971-1979. doi: 10.1016/j.ekir.2025.03.026
  • Ambrogi M, Hernandez LL, Strand DW, et. al. "A 5-HT-mediated urethral defense against urinary tract infections." Proceedings of the National Academy of Sciences of the United States of America, 122(16), (2025) e2409754122. doi: 10.1073/pnas.2409754122
  • Peschard VG, Scherzer R, Estrella MM, et. al. "Defining Kidney Health Dimensions and Their Associations with Adverse Outcomes in Persons with Diabetes and CKD." Clinical journal of the American Society of Nephrology : CJASN, 20(5), (2025) 665-675. doi: 10.2215/CJN.0000000676
  • Manrique-Caballero CL, Barasch J, Zaidi SK, et. al. "Expression and distribution of MUC1 in the developing and adult kidney." American journal of physiology. Renal physiology, 328(1), (2025) F107-F120. doi: 10.1152/ajprenal.00206.2024
  • Beenken A, Shen T, Jin G, et. al. "Spns1 is an iron transporter essential for megalin-dependent endocytosis." American journal of physiology. Renal physiology, 327(5), (2024) F775-F787. doi: 10.1152/ajprenal.00172.2024
  • Schmidt IM, Surapaneni AL, Zhao R, et. al. "Plasma proteomics of acute tubular injury." Nature communications, 15(1), (2024) 7368. doi: 10.1038/s41467-024-51304-x
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Professional Service

  • Present-2013, Professor of Medicine and Pathology and Cell Biology, and Urology, with Tenure. 
  • Present-2009, Course Director “Molecular Mechanisms”, First Year Medical School.
  • 2013 -2003, Associate Professor of Medicine and Cell Biology, with Tenure, Columbia University
  • 2003 -1994, Assistant Professor of Medicine, Columbia University, 
  • 1994 -1991, Instructor in Clinical Medicine, Columbia University, 
  • 1991 -1990, Visiting Fellow in Clinical Nephrology, Columbia-Presbyterian Medical Center 
  • 1990 -1988, Intern/ Resident in Internal Medicine, Columbia-Presbyterian Medical Center,