Richard Ho
Faculty Member
Last active: 11/10/2016

Profile

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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Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Contribution of Organic Anion-Transporting Polypeptides 1A/1B to Doxorubicin Uptake and Clearance. Lee HH, Leake BF, Kim RB, Ho RH (2017) Mol Pharmacol 91(1): 14-24
    › Primary publication · 27777271 (PubMed) · PMC5198512 (PubMed Central)
  2. Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy. Van Driest SL, McGregor TL, Velez Edwards DR, Saville BR, Kitchner TE, Hebbring SJ, Brilliant M, Jouni H, Kullo IJ, Creech CB, Kannankeril PJ, Vear SI, Brothers KB, Bowton EA, Shaffer CM, Patel N, Delaney JT, Bradford Y, Wilson S, Olson LM, Crawford DC, Potts AL, Ho RH, Roden DM, Denny JC (2015) PLoS One 10(6): e0127791
    › Primary publication · 26030142 (PubMed) · PMC4452656 (PubMed Central)
  3. Patterns and severity of vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia. Lavoie Smith EM, Li L, Chiang C, Thomas K, Hutchinson RJ, Wells EM, Ho RH, Skiles J, Chakraborty A, Bridges CM, Renbarger J (2015) J Peripher Nerv Syst 20(1): 37-46
    › Primary publication · 25977177 (PubMed) · PMC4610712 (PubMed Central)
  4. Contribution of hepatic organic anion-transporting polypeptides to docetaxel uptake and clearance. Lee HH, Leake BF, Teft W, Tirona RG, Kim RB, Ho RH (2015) Mol Cancer Ther 14(4): 994-1003
    › Primary publication · 25695959 (PubMed) · PMC4394048 (PubMed Central)
  5. Long-term use of the thrombopoietin-mimetic romiplostim in children with severe chronic immune thrombocytopenia (ITP). Bussel JB, Hsieh L, Buchanan GR, Stine K, Kalpatthi R, Gnarra DJ, Ho RH, Nie K, Eisen M (2015) Pediatr Blood Cancer 62(2): 208-213
    › Primary publication · 25345874 (PubMed) · PMC4309514 (PubMed Central)
  6. The outcome of allogeneic hematopoietic cell transplantation for children with FMS-like tyrosine kinase 3 internal tandem duplication-positive acute myelogenous leukemia. Schechter T, Gassas A, Chen H, Pollard J, Meshinchi S, Zaidman I, Hitzler J, Abdelhaleem M, Ho R, Domm J, Woolfrey A, Frangoul H (2015) Biol Blood Marrow Transplant 21(1): 172-5
    › Primary publication · 25139215 (PubMed)
  7. The impact of age and CYP2C9 and VKORC1 variants on stable warfarin dose in the paediatric population. Vear SI, Ayers GD, Van Driest SL, Sidonio RF, Stein CM, Ho RH (2014) Br J Haematol 165(6): 832-5
    › Primary publication · 24601977 (PubMed) · PMC4043918 (PubMed Central)
  8. Targeted Busulfan therapy with a steady-state concentration of 600-700‚ÄČng/mL in patients with sickle cell disease receiving HLA-identical sibling bone marrow transplant. Maheshwari S, Kassim A, Yeh RF, Domm J, Calder C, Evans M, Manes B, Bruce K, Brown V, Ho R, Frangoul H, Yang E (2014) Bone Marrow Transplant 49(3): 366-9
    › Primary publication · 24317124 (PubMed)