Department of Defense PI: Shankland 09/15/2019 – 09/14/2022
Targeting Parietal Epithelial Cells in FSGS
Our central hypothesis is that PEC biology can be influenced by external stimuli to lessen or revert the lesions caused by FSGS. The goal of
this project is to test two hypotheses: (1) that a specific combination of signaling agonists and/or antagonists will drive trans-differentiation
of PEC progenitors towards an adult podocyte fate. (2) that a specific set of signaling agonists and/or antagonists will interfere with the
detrimental “activation” of PECs, and in doing so, reduce extracellular matrix protein production.
NIA 5R01AG046231 PI: Shankland 06/15/2016-12/14/2021
Reduced Glomerular Progenitors Impair Regeneration in Aged Kidney
The need to better understand the effects of aging on the kidney is ever more important with the increasing aging population.
The grant will define how the decline in podocyte number with advancing age cannot adequately be replaced by their
neighboring parietal epithelial cell progenitors, which leads to kidney scarring.
Department of Defense W81XWH-16-1-0168 PI: Shankland 09/30/2016-09/29/2019
New podocyte-targeted treatments for focal segmental glomerulosclerosis (FSGS)
Our overall goals are to improve drug biodistribution directly to podocytes while decreasing systemicexposure to active drug,
and to demonstrate drug efficacy and safety in an animal model of FSGS. To meet these objectives we propose the following
aims: Aim 1. Optimize and characterize cyclic “sunflower” polymer kidney accumulation in a mouse model of FSGS. The goal of
this aim is to synthesize and optimize a drug delivery vehicle that preferentially distributes to and is retained in the kidney after
NIH/NIDDK 5T32DK007467 PI: Shankland 7/15/2014-6/30/2024
Research Training in Renal Disease
The overall goal is to train basic and clinical scientists in kidney-related research so that they will be ideally positioned to
successfully compete for mentored funding, and ultimately transition to research independence. We have developed four
major research training tracks (metabolic disorders and biomarkers; glomerular and tubulointerstitial diseases; clinical
epidemiology and health services research; end-stage renal disease and complications).
NIH/NIDDK 2R01DK097598-06 PI: Shankland 08/05/2014-05/31/2023
Juxta-glamerular cells serve as glomerular epithelial cell progenitors in glomerular disease
The purpose of this proposal is to study the existing problem of age-related podocyte depletion in a completely new context.
The goal is to prove that with advancing age, kidney regeneration, and thus repair, is inadequate because progenitors are
unable to replace and restore glomerular podocytes. We anticipate that the results will provide compelling evidence for a new
paradigm in aging kidneys in which recently identified progenitors are unable to adequately regenerate to replace podocytes,
which leads to glomerulosclerosis and reduced kidney function.
NIDDK UH3DK107343 PI: Shankland, Zheng 09/23/2015-08/31/2020
Rebuilding the glomerular filtration barrier by regenerating adult podocytes (Re)BuildingAKidney.org
Podocytes are cells in the kidney’s glomerular filtering units that limit the passage of proteins from the blood in to the urine. As
adults, they cannot proliferate to replace themselves, and therefore they are reliant on other stem cells for their regeneration. In
this grant, we will study such stem cells in podocyte repair to rebuild a kidney.
NIH 5U2CDK114886 MPI: Himmelfarb, Iyengar, Kretzler Co-I: Shankland 09/15/17-06/30/22
Central Hub for Kidney Precision Medicine
The overarching objective of the KPMP Central Hub is to facilitate logistics and operations required to promote scientific rigor,
patient safety, and the successful interdisciplinary team science to for major advances in kidney precision medicine.
NIH UH3TR002158 PI: Himmelfarb Co-I: Shankland 07/25/2017- 06/30/2022
A Microphysiological System for Kidney Disease Modeling and Drug Efficacy Testing
To model important human kidney diseases and promote identification of safe and effective treatments. We have established a
multidisciplinary investigative team with expertise in kidney physiology and pathology, cellular and molecular biology, systems
pharmacology and toxicology, biomarker discovery and evaluation, biomedical engineering, microfluidics, matrix biology,
genomics, computational biology, and biostatistics. In vitro models that recapitulate critical aspects of kidney physiological
function, response to injury, and repair could contribute greatly to drug discovery and development, and could ultimately
enable ‘virtual clinical trials’ for candidate therapeutics.
NIH/NIDDK PI: Shankland 09/01/2019 – 08/31/2024
Kidney Aging Impairs Progenitor and Endocrine Function
The purpose of this study is to fill in knowledge gaps in aged kidneys by identifying important mechanisms underlying the decrease in
CoRL’s number, progenitor function, endocrine phenotype and function. To achieve this, the following specific aims are proposed: (1) Test
the hypothesis that senescence impairs the facultative stem cell function of cells of renin lineage (CoRL) during aging. (2) Test the
hypothesis that chronic inflammation reduces the endocrine phenotype and function of aged cells of renin lineage. (3) Test the hypothesis
that mitochondrial changes in the aged kidney lowers the number of cells of renin lineage.