[K01] Investigating Mitochondrial DNA as a Biomarker and Therapeutic Target in Chronic Kidney Disease
Ente: National Institute of Diabetes and Digestive and Kidney Diseases
Scadenza: 2031-05-31
Importo max: 148.596 EUR
Paese: US
Descrizione
Project Summary
This is a submission of a K01 application by Dr. Armin Ahmadi, PhD, a postdoctoral fellow at University of
California San Diego (UCSD). Through this proposal Dr. Ahmadi intends to establish himself as an independent
investigator studying the intersection of mitochondrial dysfunction, microvascular health, and physical functioning
in chronic kidney disease (CKD). This project aims to establish cell free mitochondrial DNA (cf-mtDNA) as a
novel biomarker of kidney and vascular dysfunction in CKD and to evaluate nicotinamide riboside (NR) as a
potential therapeutic strategy.
Candidate: Dr. Ahmadi’s training objectives include 1) to become proficient in the measurement of mtDNA and
noninvasive microvascular techniques and translation to patient-oriented research; 2) to gain expertise in
advanced statistical methods relevant to clinical trials; and 3) to learn the necessary skills to develop an
independent research program and to design and lead clinical trials. Dr. Ahmadi will accomplish these objectives
through mentorship, coursework, and participation in workshops. He has assembled a multidisciplinary team of
scientists including Dr. Joachim Ix, an expert clinical trialist (primary mentor), Dr. Rakesh Malhotra, a nephrologist
and a leader in the field of microcirculation assessment and interpretation in humans (co-mentor); Dr. Mark
Hepokoski, an expert in mitochondrial biology and a pioneer in cf-mtDNA measurements (co-mentor) and Dr.
Ronit Katz, a PhD level biostatistician who focuses her work on clinical trials (statistical mentor). In addition, Dr.
Mary McDermott, an expert in metabolic interventions for peripheral vascular disease and with NR trial expertise.
Research: Current CKD biomarkers provide limited insight into disease progression and vascular dysfunction,
two key contributors to CKD-related complications. Dr. Ahmadi’s overall hypothesis is that cf-mtDNA may be
used as a biomarker of kidney and vascular dysfunction providing mechanistic insight on the relationship
between the loss of kidney microvasculature integrity that lead to reduced kidney function and mitochondrial
dysfunction. In Aim 1, Dr. Ahmadi will evaluate the relationship between cf-mtDNA and skin microvascular
measurements among 250 individuals with CKD. In Aim 2a, Dr. Ahmadi will evaluate the association of circulating
and urinary cf-mtDNA with CKD progression in 250 participants with CKD. In Aim 2b, Dr. Ahmadi will determine
the associations between urinary and plasma cf-mtDNA with kidney vascular health in 75 individuals with
available kidney biopsy. Lastly, in Aim 3, Dr. Ahmadi will evaluate the feasibility and efficacy of 12 weeks of
nicotinamide riboside (NR) supplementation in modifying circulating cf-mtDNA levels, microvascular function,
and physical function in CKD among 30 CKD subjects. Both the training and research plans will lay the
groundwork for use of mitochondria-related biomarkers to assess kidney and microvascular dysfunction in CKD
in cl
Istituzione: UNIVERSITY OF CALIFORNIA, SAN DIEGO
PI: Armin Ahmadi
Progetto: 1K01DK147652-01
Settori: National Institute of Diabetes and Digestive and Kidney Diseases
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