Postdoctoral Fellow

UT Southwestern Medical Center
Salary commensurate with experience
September 09 2017
Position Type
Full Time
Organization Type
Job Type

<p><b>Postdoctoral Opportunity in Targeting Mitochondrial Protein Kinases for Metabolic Diseases </b></p> <p>A postdoctoral position is currently open in the laboratory of Dr. David Chuang in the Department of Biochemistry at UT Southwestern Medical Center to investigate mitochondrial protein kinases as drug targets for severe metabolic diseases. Recent advancements have implicated that elevated branched-chain amino acids (BCAAs) leucine, isoleucine and valine as a group is an important biomarker as well as a putative causal factor in human diseases. These include obesity, type 2 diabetes, cancer, sarcopenia, along with neurological and cardiovascular diseases. The mitochondrial protein kinase of interest, i.e. branched-chain keto acid dehydrogenase kinase (BDK), negatively regulates the branched-chain keto acid dehydrogenase complex (BCKDC), the rate-limiting step in BCAA catabolism, by reversible phosphorylation.</p> <p>Our laboratory recently identified and synthesized several small-molecules that allosterically inhibit BDK activity with high potency and selectivity (<i>PNAS</i>.110:9728-33, 2013; <i>JBC. </i>289:20583-93, 2014). Treatments of pre-diabetic <i>ob/ob </i>mice and diet-induced obese mice with a novel BDK inhibitor BT2 [3,6-dichlorobrenzo(b)thiophene-2-carboxylic acid] robustly lower circulating BCAAs and corresponding keto acids (BCKAs) concentrations, resulting in improved glucose tolerance and insulin sensitivity as well as reduced hepatic steatosis. Moreover, we have recently produced CRISPR/Cas9 knock-in mouse models for Maple Syrup Urine Disease (MSUD), a severe inherited metabolic disorder in BCAA degradation caused by mutations in the BCKDC. The accumulation of BCAAs and their toxic metabolites BCKAs leads to often-fatal ketoacidosis, neurological derangements and mental retardation. Our plans are to develop a second generation of more efficient BDK inhibitors. We will test the central hypothesis that targeting mitochondrial BDK is an effective pharmacological approach to treating important metabolic diseases such as obesity, type 2 diabetes and MSUD.</p> <p>Candidates must hold a most recent Ph.D. degree. Experience in metabolic and/or pathologic studies in mice or rats and treatments with small molecules leading to publications in peer-reviewed journals are recommended.</p> <p>Interested individuals should send a CV, statement of interests and a list of three references by email to:</p> <p>David Chuang, Ph.D.</p> <p>Department of Biochemistry UT Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-9038</p> <p>Email:</p> <p><i>UT Southwestern Medical Center is an Affirmative Action/Equal Opportunity Employer. Women, minorities, veterans and individuals with disabilities are encouraged to apply.</i></p> <p>&nbsp;</p>

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