Dr Michael Sorich

My primary interest is in applied pharmaceutical and biological modelling/informatics. Research projects that I have made a significant contribution to include a clinical trial of analgesia following third molar extraction, molecular modelling of drug metabolism enzymes, development of a bioinformatics algorithm to improve genotyping, development of methods for computer-aided lead identification and optimisation, and metabolic profiling of disease and pharmaceutical effects. In 2003 I was awarded a NHMRC CJ Martin Postdoctoral Research Fellowship. During this time I worked at St Jude Children’s Research Hospital in Memphis USA, undertaking transcriptomic and proteomic research to gain insight into resistance and response of leukaemic cells to chemotherapy. My current research focuses on understanding the causes and pathophysiology of autism and subsequently developing therapeutic interventions that are targeted to the underlying biology

I am course co-ordinator of Pharmacy Practice 2 and also teach into a number of other courses, predominantly in the pharmacy program.

Australasian Pharmaceutical Science Association (APSA)

Australasian Society of Clinical and Experimental Pharmacology and Toxicology (ASCEPT)

International Society for the Study of Xenobiotics (ISSX)

QSAR and Modelling Society

Adelaide Pharmacology Group

PhD, University of South Australia, 2004
“Molecular modelling of UDP-glucuronosytransferase”
This project involved both in vitro and in silico experimentation on UDP- glucuronosyltransferase (UGT), an enzyme that plays an important role in the metabolism of many endogenous chemicals and drugs. Inhibition constants and the presence of atypical enzyme kinetics were determined for a broad selection of chemicals against UGT1A1 in vitro. A wide variety of molecular modelling techniques - including quantitative structure-activity relationships, pharmacophore perception and quantum chemistry – were applied to better understand the structural features of chemicals that influence binding affinity, catalysis and site of regioselectivity for a range of UGT isoforms. In many cases, this also involved the design of new molecular modelling techniques that were particularly suited to the unique nature of this enzyme family.

Bachelor of Pharmacy (Honours), University of South Australia, 1999
“Multiple-dose comparison of dextropropoxyphene/paracetamol combination and paracetamol alone after third molar dental extractions”
This study was a randomized, double blinded, parallel, and controlled clinical trial involving 120 patients and two treatment study arms. I was responsible for the designing the study, organising of all trial drugs and assessment materials, the enrolment and follow-up of all patients, and the statistical analysis of the data.

Bachelor of Pharmacy, University of South Australia, 1998

• Pharmacogenomics / personalised medicine
• Drug metabolism
• Molecular modelling / computer aided drug design
• Metabolomics / proteomics / transcriptomics

Sorich MJ, Pottier N, Pei D, Yang W, Panetta JC, Pui CH, Cheok MH, Relling MV, Evans WE. In vivo Response to Methotrexate forecasts Outcome of Acute Lymphoblastic Leukemia and has a Distinct Gene Expression Profile. PLOS Medicine 2008; 5(4): e83 (Impact Factor 13.75)

Sorich MJ, Smith PA, McKenzie P, Miners JO, McKinnon RA. Recent advances in UDP Glucuronosyltransferase substrate in silico modelling. Current Drug Metabolism (in preparation; Impact Factor 4.6)

Sorich W, Stranks S, Kuruvila M, Kowalski S, Sorich MJ. Vitamin B12 deficiency in the elderly using metformin: prevalence and relationship to potential risk factors. Journal of Pharmacy Practice and Research 2008; 38(2): 111

McKinnon RA, Ward MB, Sorich MJ. Barriers to the clinical implementation of pharmacogenomics. Therapeutics and Clinical Risk Management (in press)

Ward, MB, Sorich MJ, McKinnon RA. Cytochrome P450 Part 2: Genetics of Inter-Individual Variability. Journal of Pharmacy Practice and Research 2008; 38(3): 226-229

Sykes MJ, Sorich MJ, Miners JO. In silico prediction of non-specific microsomal binding. Journal of Chemical Information and Modeling 2006; 46(6): 2661-2673 (Impact Factor: 2.9)

Mittal R, McKinnon RA, Sorich MJ. Effect of steric molecular field settings on CoMFA predictivity. Journal of Molecular Modeling 2008; 14(1): 59-67 (Impact Factor 1.4)

Dias M, Mittal R, McKinnon RA, Sorich MJ. Systematic statistical comparison of CoMSIA molecular fields for 3D-QSAR. Jounal of Chemical Information and Modeling 2006; 46(5): 2015-2021 (Impact Factor 2.9)

McKinnon RA, Sorich MJ, Ward, MB. Cytochrome P450 Part 1: Multiplicity and Function. Journal of Pharmacy Practice and Research 2008; 38(1): 55-57

Sorich MJ, Smith PA. Predicting drug metabolism in silico. Current Topics in Medicinal Chemistry 2006; 6(15): 1567-8 (Editorial; Impact Factor 4.4)

Sorich MJ, McKinnon RA, Miners JO, Smith PA. The importance of local chemical structure for chemical metabolism by human UDP-glucuronosyltransferase. Jounal of Chemical Information and Modeling 2006; 46(6): 2692-2697 (Impact Factor 2.9)

Haddy C, McKinnon R, Sorich M, Ward M,. Pharmacogenomics. in Australian Pharmaceutical Formulary, Sansom LN. Ed. 20th Edn, Australian Medicines Handbook, Adelaide pp248-250 (2006)

Sorich MJ, McKinnon RA, Miners JO, Winkler DA, Smith PA. Rapid prediction of chemical glucuronidation using quantum-chemical descriptors derived with the electronegativity equalization method. J Med Chem 2004; 47 (21): 5311-5317 (Impact Factor: 5.1)

Smith PA, Sorich MJ, Low LSC, McKinnon RA, Miners JO. Towards integrative ADME prediction: past, present and future trends in modelling metabolism by UDP glucuronosyltransferases. Journal of Molecular Graphics and Modeling 2004; 22(6): 507-517 (Impact Factor: 3.0)

Sorich MJ, Osborne G, Jarvis DA, Macintyre PE, Sprigg J, Doecke CJ. Multiple-dose comparison of dextropropoxyphene/paracetamol combination and paracetamol alone after third molar dental extractions. Journal of Pharmacy Practice and Research 2004; 34(1): 22-25

Sorich MJ, Miners JO, McKinnon RA, Smith PA. Multiple pharmacophores for the investigation of human UDP-glucuronosyltransferase isoform substrate selectivity. Mol Pharmacol 2004; 65(2): 301-308 (Impact Factor: 5.1)

Miners JO, Smith PA, Sorich MJ, McKinnon RA, Mackenzie PI. In vitro and in silico approaches for prediction of drug metabolism parameters for drugs eliminated by glucuronidation. Ann Rev Pharmacol Toxicol 2004; 44: 1-25 (Impact Factor: 21.1)

Smith PA, Sorich MJ, McKinnon RA, Miners JO. Pharmacophore and quantitative structure activity relationship (QSAR) modelling: Complementary approaches to the rationalisation and prediction of UDP glucuronosyltransferase 1A4 (UGT1A4) substrate selectivity. J Med Chem 2003; 46(9): 1617-1626 (Impact Factor: 5.1)

Sorich MJ, Miners JO, McKinnon RA, Winkler DA, Burden FR, Smith PA. Comparison of linear and non-linear classification algorithms for the prediction of chemical metabolism by UDP-glucuronosyltransferase isoforms. J Chem Inf Comp Sci 2003; 43(6): 2019-2024 (Impact: 2.8)

Smith PA, Sorich MJ, McKinnon RA, Miners JO. In silico insights: chemical and structural characteristics associated with UDP-glucuronosyltransferase (UGT) substrate selectivity. Clin Exp Pharmacol Physiol 2003; 30 (11): 836-840 (Impact Factor: 1.7)

Sorich MJ, Smith PA, McKinnon RA, Miners JO. Pharmacophore and quantitative structure activity relationship modeling of UDP-Glucuronosyltransferase 1A1 (UGT1A1) Substrates. Pharmacogenetics 2002; 12: 635-646 (Impact Factor: 6.4)