David A Rudnick, MD, PhD

Research interest

Metabolic Regulation

Complications

Category(ies) of Research

Basic

Clinical

Descriptor of Research

My research-program focuses on the pathogenesis of liver diseases and the mechanisms that mediate regenerative-recovery from those injuries. We use partial-hepatectomy (PH) and cell and mouse models of α1antitrypsin deficiency (ATD) to study these questions.

Our work has provided new information about how host metabolism is both affected by and a mediator of liver injury and recovery from injury. We previously showed that hypoglycemia and hepatic steatosis are characteristic of the metabolic response to PH and generate regenerative signals whose disruption delays regeneration. We also reported an epigenetic signature of PH-induced hepatic regeneration and defined metabolic influences on that signature. Those studies led to our identification of factors whose regulation is influenced by metabolism, and a report describing interactions between diet and liverspecific, drug-induced activation of PPAR on hepatic mitochondrial gene expression.

In earlier work with Dr. Perlmutter I reported the first characterization of liver regeneration in the PiZ mouse model of ATD-liver-disease. That work led to a novel conceptual model for the pathogenesis of hepatocellular carcinoma in ATD, with subsequent work validating that model.

I recently reestablished a collaborative partnership with Perlmutter that has led to a new RO1-funded project bringing together my group’s expertise in metabolic effects of and on liver injury and Perlmutter’s expertise in ATD-liverdisease. This partnership has already led to novel observations implicating insulin signaling and mitochondrial impairment in the pathogenesis of ATDliver-disease, and, therein, our current research efforts testing novel therapies targeting ATD-liver-disease pathogenesis.

PubMed