We culture mouse embryonic stem cells and perform gene targeting by using Crispr/Cas9 and HDR. Our experience with genome modification allows us to generate unique models to interrogate disease models with precision.
Crispr-Cas9 based gene editing offers genome editing with unparalleled specificity and speed. All trainees learn this technology which we apply in cell lines and stem cells.
Stem Cell Biology
The ability to generate patient-specific pluripotent stem cells gives hope that we can grow replacement kidneys ‘in a dish’ that can someday be used in transplantation. Understanding the potential of kidney organoids is a major focus.
We are leveraging single cell RNA-seq approaches including DropSeq, sNucDropSeq, InDrops and FACS-Seq to generate transcriptional atlases of kidney organoids and adult kidney in health and during the course of disease.
Over 100,000 people per year develop kidney failure in the US and most are treated with dialysis therapy. While life-saving, this procedure is costly, inconvenient and accelerates heart disease.
An average dialysis patient has a 1 in 5 chance of dying every year. Paying for dialysis costs 7 percent of the entire Medicare budget, even though these patients make up only 1 percent of the Medicare population.
In The Humphreys Lab we are developing new and innovative treatments to help patients with kidney disease. We are using human stem cells to generate kidney organoids in a dish, with a goal of one day transplanting them into patients with kidney failure. We also study the kidney’s ability to regenerate itself so that we can harness this ability for therapeutic uses.
Genetic mouse models
We have created 5 transgenic and 3 knockin mouse lines with 6 more in production
We are using gene editing to create novel KO and KI iPS and mouse ES lines
We use RNA-Seq to expression profile kidney cell types
Human kidney single cell RNA-seq
We perform DropSeq and InDrops on organoids and kidney biopsies
Benjamin D. Humphreys MD, PhD
monica Chang-panesso MD
Jeff Lai MD
Yoshiharu Muto, MD
Yuhei Kirita ,MD
Sai Mukund Ramakrishnan
Zhao Sun PhD
Kohei Uchimura PhD
Haojia Wu PhD
Support Our Mission to Cure Kidney Failure
The field of single cell transcriptomincs by RNA-Seq at high-throughput scale is revolutionizing biological investigation. Microfluidic droplet technologies allow co-encapsulation of a cell, barcoded DNA oligonucleotides and cell lysis buffer within a tiny droplet of about 2 nanoliters. These transformative approaches allow for parallel processing of thousands of cells with great efficiency and precision and[…]
Scientists have implicated a type of stem cell they believe is responsible for calcified blood vessels common in patients with chronic kidney disease. The research will guide future studies into ways to block minerals from building up inside blood vessels and exacerbating atherosclerosis, the hardening of the arteries. The study, led by researchers at[…]
A funded postdoctoral position is available in the Division of Nephrology at Washington University in St. Louis. The Humphreys laboratory (http://humphreyslab.com/) investigates the cellular and molecular mechanisms of adult kidney injury and repair. We are exploring the role of developmental signaling pathways (Hh, Wnt) in paracrine signaling during kidney injury and fibrosis with potential future[…]
Here is an opinion piece I wrote for the Washington Post from a series entitled, “Compensation for organ donors,” edited by Robert Gebelhoff. From the introduction: “Last month, a group of researchers published in the American Journal of Transplantation a cost-benefit analysis for a government-funded program that would offer $45,000 to living kidney donors. They[…]
In this paper published in Cell Stem Cell, we identified Gli1 as a marker for resident mesenchymal stem cells across organs (Kidney, Heart, Lung, Liver, Bone Marrow). Using lineage analysis, we show that chronic injury drives these cells to proliferate and differentiate into scar-secreting myofibroblasts. Rafael Kramann, the first author, then genetically ablated these Gli1+ progenitors[…]