Current Funding

 

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

injection.

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.

Pending

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.