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) Analyzing the lineage of kidney epithelial, mesenchymal and stem cells during homeostasis, injury and repair and (2) understanding the genetic and epigenetic regulation of epithelial cell differentiaion and proliferation after injury. www.twitter.com/HumphreysLab

Humphreys Lab News

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 have developed a method for distinguishing between renal repair by extratubular progenitor cells and renal epithelial cells. We have used a transgenic mouse in which the Six2 promoter drives Cre recombinase in collaboration with the Bonventre and McMahon groups at Harvard. In this strain, Cre is expressed transiently in renal epithelial precursors during development, with no Cre expression in the adult or re-expression after injury. We crossed this Six2-Cre mouse with a reporter strain in which Cre-dependent removal of a stop sequence causes constitutive and heritable expression of a marker gene such as alkaline phosphatase or DsRed. In these mice, renal epithelial cells, from Bowman’s capsule to the distal convoluted tubule, are heritably labeled but extratubular cells such as interstitial cells, remain unlabeled. To test whether unlabeled cells could contribute to the epithelial lineage during renal repair, we perform injury experiments and allow kidneys to recover. By examining repaired tubules for dilution of label vs. retention of label, we are able to assess whether any unlabeled cells contribute to repair of damaged nephrons.

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