Current Research Support

NIH/NIDDK 1 UC2 DK126006 PI: Shankland 09/01/2020-05/31/2025

Cell-specific delivery of novel therapies to enhance and repair glomerular regeneration

The primary goal of this study is to change the treatment paradigm for diseases affecting the podocytes, cells that physically filter the blood

to form the urine, by combing therapeutics development with cell-specific delivery to enhance the natural ability of the body to repair and

regenerate these highly specialized cells.

Department of Defense W81XWH2010440 PI: Punn Co-I: Shankland 09/30/2020 – 09/29/2023

Engineering technologies for improved treatment of FSGS

The major goals of this proposal are to develop technologies for targeted drug delivery to specific kidney cell populations for FSGS

treatment.


NIH/NIDDK PI: Shankland 02/11/2020-12/31/2023

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 lower the number of cells of renin lineage.

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.

NIH/NIDDK 2R01DK097598-06 PI: Shankland  08/05/2014-05/31/2023                                                                            

Juxta-glomerular 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.

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 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 the 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 Research Support

NIH/NIDDK R01 Shankland & Wessely 07/01/2022 – 06/30/2027

Autocrine and paracrine podocyte signals decrease glomerular function/health in aged kidneys

The major goal of this proposal is to prove that in the aged kidney, podocytes are central to the many glomerular changes. This research

will seek fundamental knowledge regarding the reasons why kidneys age so that these pathways can be potentially modified when

superimposed stress is added to an aged kidney such as disease and the surgical loss of kidney mass.

NIH U2CDK114886 MPI: Himmelfarb, Iyengar, Kretzler Co-I: Shankland 07/01/22-06/30/27

Central Hub for Kidney Precision Medicine (competitive renewal)

The overarching objectives of this Central Hub renewal application for the KPMP are to 1) Build, support, and maintain a Central Hub

infrastructure that can support all KPMP activities, and capably provide leadership and governance for KPMP; 2) Provide administrative

support, project management, and scientific leadership for all aspects of KPMP day to day function; 3) Build, support, and maintain an

inclusive, collaborative culture within KPMP that continuously honors and values the contributions of study participants, 4) Administer an

Opportunity Pool of funds to catalyze new partnerships, maintain KPMP dynamism, and address any gaps relevant to achieving KPMP

goals; 5) Support seamless integration of workflow between Recruitment Sites, Tissue Interrogation Sites, KTACC, and Opportunity Pool

funded sites; and 6) Coordinate interactions with the KPMP central IRB, Data Safety and Monitoring Board, Consortium Management

Board, and the NIDDK.

R01 AG079935 PD/PI: Shankland (contact) and Wessely (MPI) 09/01/2022 – 08/31/2027

The Intersection of Podocyte Aging and Disease

The major goal of this proposal is to prove that disease progression is because podocyte injury is synergistic with biological aging. Specific

Aim #1 will prove that injury to podocytes causes a premature aging podocyte phenotype, and that age predisposes podocytes to injury to

a more severe outcome. This will be achieved by testing the following hypotheses: (i) Injury to young podocytes accelerates their

aging/senescent phenotype; (ii) Injury to aged podocytes augments senescence damage. (iii) Removing senescent podocytes in glomerular

disease improves short- and long-term disease outcomes. Specific Aim #2 will prove that the mechanisms of podocyte injury and that of

aging overlap, and are compounded when superimposed on one another. We will test the following hypotheses: (i) The transcriptomic

changes in individual injured podocytes are similar to or augmented compared to individual aged podocytes; (ii) Accelerated podocyte

injury in aged kidney is due to paracrine signaling resulting from a podocyte senescent associated secretory phenotype (SASP).