The VICC.ORG Directory of Doctors, Healthcare Providers & Researchers

Richard Ho, M.D., MSCI

Associate Professor of Pediatrics (Pediatric Hematology and Oncology)
VICC Member
Pediatric Hematologist/Oncologist

Profile

Dr. Ho is a pediatric fellowship-trained hematologist/oncologist whose current research focuses on the molecular mechanisms by which drug transporters contribute to overall drug disposition and interindividual response to drug therapy. The main focus of Dr. Ho's research centers on the identification and functional characterization of naturally occurring polymorphisms in drug transport proteins as they relate to drug disposition.
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Dr. Ho is a pediatric fellowship-trained hematologist/oncologist whose current research focuses on the molecular mechanisms by which drug transporters contribute to overall drug disposition and interindividual response to drug therapy. The main focus of Dr. Ho's research centers on the identification and functional characterization of naturally occurring polymorphisms in drug transport proteins as they relate to drug disposition. To this extent, the focus is on pharmacogenetics, the study of the role of inheritance in the individual variation in drug response. Dr. Ho is currently studying several transport proteins important to the disposition of a number of chemotherapeutics agents and include such transporters as the multi-drug resistance associated proteins (MRPs), the bile salt export pump (BSEP), and the breast cancer related protein (BCRP).

Education

  • M.D.-Vanderbilt University, Nashville, TN, 1997
  • Pediatric Resident-Vanderbilt University Medical Center
  • Research Fellow-Pediatric Hematology-Oncology and Clinical Pharmacology; Vanderbilt University
  • Clinical Fellow-Pediatric Hematology-Oncology, Vanderbilt University

Research Specialty

Drug Uptake Transporters and Chemotherapy Disposition

Research Description

Our research program focuses on the molecular mechanisms by which drug transporters contribute to overall chemotherapy disposition and interindividual response to drug therapy in cancer therapy. Drug transport proteins have important roles in modulating the absorption, distribution, and excretion of many drugs and drug metabolites as well as endogenous substances. They tend to be highly expressed in tissues of importance to drug disposition, including the liver, intestine, kidney and at the blood:brain barrier. To this extent, a major focus in my lab centers on the contribution of specific drug uptake transporters, in particular the organic anion transporting polypeptide (OATP) family and bile acid uptake transporters, to the disposition of pediatric chemotherapeutic agents. In addition, another area of major focus is cancer pharmacogenetics, the study of the role of inheritance in the individual variation in chemotherapy response. Projects are primarily laboratory based with translational promise and rely on background knowledge in the fields of molecular biology and clinical pharmacology. We utilize a number of in vitro techniques to study these transporter proteins, including vaccinia-based expression systems for functional transport studies, drug screening, and drug inhibition studies, protein expression studies utilizing western analysis, immunohistochemistry and immunofluorescent confocal microscopy, and generation of polarized stable cell lines for directional transport studies and comprehensive kinetic analysis. We have also integrated animal models utilizing recently generated knockout mice for various transporter genes into our research program for in vitro:in vivo correlative data in our drug disposition studies.

Moreover, our research has important implications for drug discovery and experimental therapeutics. ADME (absorption, distribution, metabolism and excretion) deficiency is one of the major causes of failure during drug development. In vitro ADME screening of potential lead compounds and drug candidates in the early discovery phase has been employed as a more cost-effective approach to identify compounds that have unfavorable drug-like characteristics. Many compounds with promising pharmacological characteristics never become drugs because they have poor solubility, quickly degrade in biological fluids and tissues or rapidly metabolized in the liver. Utilizing our in vitro screening transport and detailed studies of kinetic analysis, we are able to identify potential drug compounds as substrates for a complement of drug uptake and efflux transporters, which may have important implications not only for drug disposition in vivo, but also for drug toxicity, efficacy and tissue targeting. Furthermore, as many of the transporters we study are known to be polymorphic, we have the ability to assess transporter polymorphisms for differential transport of drugs and/or drug metabolites, which may have significant consequences for determining the interindividual response to anticancer agents.

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Clinical Interest

Clinical pharmacology
Drug disposition and toxicity
Pharmacogenetics and pharmacokinetics
Oncology

Publications


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