The Humphreys Lab



The mission of the Humphreys Lab is to understand the cellular and molecular mechanisms of kidney repair and thereby identify new therapeutic strategies for humans suffering from kidney disease. The work encompasses two main areas: (1) Developing stem cell-based approaches to treat kidney disease in humans and (2) understanding the mechanisms of kidney repair and recovery after injury. www.twitter.com/HumphreysLab

Humphreys Lab News

April, 2014: Congratulations Dr. Rafael Kramann, postdoctoral fellow in the lab, for winning the 2014 ERA-EDTA Young Investigator Award!
April, 2014: We have published pericyte and myofibroblast-specific transcriptomes in kidney fibrosis, also using the translational profiling approach and a novel transgenic mouse line. See article in JASN.
March, 2014: Translational profiles of four critical cell types in acute kidney injury, just published in JCI. A comprehensive resource to identify new biomarkers and therapeutic targets, and a powerful technique for isolation of cell-specific RNA.
February, 2014: "Pharmacologic Quiescence" is a new strategy to protect against Acute Kidney Injury - our new paper was selected as an Editor's Pick. This work is first to implicate CDK4/6 as critical proliferative switch in proximal tubule epithelia, and suggests a novel therapeutic strategy.
November, 2013: A molecular mechanism to help explain the epidemiological link between AKI and risk of future CKD/kidney failure, according to our work published in JCI.
October, 2013: Our new article in PNAS uses lineage tracing of differentiated cells to define how injured tubules repair.
September, 2013: A very successful Stem Cells and Kidney Regeneration ISN Forefronts meeting was held in Florence, Italy September 12-15, chaired by Paola Romagnani and Ben Humphreys.
May, 2013:Congratulations MatriTarg Laboratories for winning the 2013 Dean's Health and Life Sciences Challenge!
May, 2013:Congratulations Hitesh for being accepted to graduate school!
Congratulations to Mari for receiving Honors on her Senior Thesis for the Harvard Department of Stem Cell and Regenerative Biology!
April, 2013: Continuing on their recent successes, an effort headed by Derek DiRocco, PhD and with Rafael Kramann, MD, was chosen from a Harvard-wide competition as finalists in the 2013 Dean's Health and Life Sciences Challenge, for their application "MatriTarg Laboratories" aimed at discovering innovative new treatments for solid organ fibrosis. See the announcement in the Harvard Gazette and the BWH Website
March, 2013: Derek DiRocco, PhD and Rafael Kramann, MD, were each winners in the HSCI Image Contest!
January, 2013: Omar Maarouf, MD receives BWH Department of Medicine Renal Fellow of the year. Congratulations Omar!
January, 2013: Ben Humphreys, MD, PhD receives American Heart Association Established Investigator Award.
December, 2012: Radostin Penchev is accepted to medical school. Congratulations!
November, 2012: Ivica Grgic, MD wins "Top Oral Abstract by a Trainee" at American Society of Nephrology National Meeting for his oral presentation, "New Genetic Tool for the Study of Pericytes and Perivascular Fibroblasts."
October, 2012: HSCI Kidney Program Retreat The HSCI Kidney Program hosted a very successful retreat featuring local speakers plus visiting scholars Lloyd Cantley, MD (Yale) and HSCI Distinguished Speaker Melissa Little, PhD (University of Queensland).
May, 2012: Humphreys Lab wins FASEB 2012 Bio-Art Competition for visualizing podocyte foot process by fluorescence microscopy. The competition sought "captivating, high resolution images that represent the cutting edge of 21st century biomedical research."

Genetic Analysis of Kidney Injury and Repair

Lineage tracing during renal repair. A major current focus of the lab is to investigate the lineage relationships among cell types during renal repair to assess whether adult stem cells contribute to repair. We use Cre-Lox technology to genetically tag kidney cells and analyze their fate during kidney injury and repair. We have created new Cre driver knocking and transgenic lines for this purpose, and our studies conclusively demonstrate that proximal tubule epithelial cells undergo dedifferentiation after injury, resulting in tubule repair without the presence of an extra tubular or intratubular stem cell population. These results have important implications for how to develop novel strategies to prevent injury and accelerate repair.





High Resolution Kidney Imaging

Podocyte Foot Process Visualization by Fluorescence Microscopy. Our laboratory has deep expertise with in vivo reporter alleles and currently we are taking advantage of the strong epifluorescent signal some of these fluorophores provide to generate high resolution subcellular images. For example, this picture shows podocyte foot processes imaged for the first time using fluorescence microscopy in a study led by postdoctoral fellow Ivica Grgic, MD. Sporadic tdTomato reporter activation within the podocyte population allowed visualization down to the tertiary foot process level because the neighboring podocytes did not express tdTomato, enhancing the optical contrast between labeled and unlabeled foot processes. This technical advance should allow new approaches to understand podocyte morphogenesis and differentiation in devlopment, tracing of putative podocyte progenitor populations and the subcellular analysis of podocyte foot process proteins. Grgic et al., JASN 2012, in press.

Multipotent Intratubular Stem Cells

Telomerase expression in kidney. In other studies, we have characterized Telomerase expression in the kidney using transgenic reporters with D. Breault, CHB, to investigate whether these might mark stem cells. Our analysis indicates that a heterogeneous population of cells, nearly all in the renal papilla, express telomerase, but none of them have stem or progenitor characteristics.





Recent Publications