Keigo Machida, PhD

Hepatitis C Virus (HCV) is a “silent stalker” in infected people, who can develop hepatocellular carcinomas (HCC) decades later. Our short-term goal is to study three areas:

(i) Host-pathogen interactions to identify the mechanism of HCV-associated HCC

(ii) Molecular virology of lymphotropic HCV in viral persistence and pathogenesis

(iii) Cancer biology in liver oncogenesis generated from tumor-initiating cells (TICs: “bad seeds” of treatment-resistant HCC) induced by interactions between environmental factors (alcohol, obesity) and HCV.

Our lab’s long-term goal is to test new therapeutic modalities for HCC in HCV-infected patients with alcoholism and/or obesity.

Our experience and resources on TICs have provided a unique opportunity to functionally dissect the alcohol-mediated self-renewal of liver TICs via TLR4 signaling. The p53 tumor suppressor acts as a barrier against stem cell proliferation, and inactivation of p53, or its stabilizing partner NUMB (cell fate decision molecule), leads to expansion of TICs. Although treatment efficacy of HCV has been dramatically improved in recent years, the incidence of HCV-associated HCC keeps rising due to the prevalence of obesity, alcoholism and illicit drug usage in HCV patients. Thus, we will continue our research on the development of new therapeutic modalities for HCC.

• Japan Society for the Promotion of Science: Scholarship, 1998
   – 2001
• Asian Pacific Association for the Study of the Liver (APASL): Young Investigator Award, 2007
• Research Center for Liver Diseases: USC Research Center for Liver Diseases Pilot Funding Award, 2007
   – 2007
• Liver Meeting of AASLD: Presidential Poster of Distinction, 2008
• American Cancer Society (ACS): Research Scholar, 2011
   – 2016

• University of Tokyo, School of Medicine, Tokyo, Japan — Ph.D. — 03/2001 — Molecular Immunology
• University of Southern California, Los Angeles, CA — Post-doc — 05/2003 — Molecular Virology
• Howard Hughes Medical Institute, Los Angeles, CA — Post-doc — 08/2005 — Cancer Biology

• LncRNA with MSI2 and super-enhancer in liver cancer stem cells induced by alcohol
  NIH · R21AA025470 · Sep 15, 2018 – Aug 31, 2021 · Role: Principal Investigator
• NANOG-positive cancer stem cells in liver oncogenesis induced by alcohol and HCV
  NIH · R01AA025204 · Sep 1, 2017 – May 31, 2022 · Role: Principal Investigator
• Southern California Research Center for ALPD and Cirrhosis
  NIH/NIAAA · P50 AA11999 · Jan 1, 2015 – Dec 31, 2019 · Role: Co-director of Animal Core Facility and Project 3 leader
• Nanog-positive cancer stem cells in and liver oncogenesis by alcohol and HCV
  NIH · R01AA018857 · Sep 15, 2009 – Aug 31, 2015 · Role: Principal Investigator

• hepatocellular carcinomas (HCC)
• cancer stem cells (tumor-initiating cells)
• Hepatitis C Virus (HCV)
• Alcoholic liver disease (ALD)
• Pluripotency transcription factor (NANOG)
• Toll-like receptor 4 (TLR4)
• Obesity
• Circulating tumor cells (CTC)
• Liver cancer
• Host-pathogen interactions

• Terrault, Norah
• Ou, Jing-Hsiung
• Tsukamoto, Hidekazu
• Lenz, Heinz-Josef
• Chai, Yang
• El-Khoueiry, Anthony