Alan Dombkowski, Ph.D.
Department of Pediatrics
Division of Clinical Pharmacology
Wayne State University School of Medicine
Children’s Hospital of Michigan
3901 Beaubien Blvd. Room 3N47
Detroit, MI 48201
- Functional genomics
- Semi-conductor sequencing
- Computational biology
- Algorithm development
The central theme of my research is the integration of functional genomics and computational methods to elucidate molecular mechanisms of disease and to identify potential therapeutic targets. We develop and apply computational methods to leverage the depth and dimensionality of “omics” data derived from a range of molecular levels, e.g. transcript, microRNA, epigenetic, and protein. The methods are typically focused on characterization of cellular pathways and signaling events involved in disease progression and pathology. We are engaged in collaborative studies associated with a variety of cancers and tuberous sclerosis complex. In particular, we are investigating microRNA dysregulation and epigenetic events that occur in response to alterations of the mTOR pathway. Our work with benign tumors that arise in tuberous sclerosis complex (TSC) patients may help determine why some mutations in the mTOR pathway lead to malignancies while others result in benign lesions.
Huang YW, Gu F, Dombkowski A, Wang LS, Stoner GD. Black raspberries demethylate Sfrp4, a WNT pathway antagonist, in rat esophageal squamous cell papilloma. Mol Carcinog. 2016;55:1867-75.
Edwards H, Rubenstein M, Dombkowski AA, Caldwell JT, Chu R, Xavier AC, Thummel R, Neely M, Matherly LH, Ge Y, Taub JW. Gene Signature of High White Blood Cell Count in B-Precursor Acute Lymphoblastic Leukemia. PLoS One. 2016;11:e0161539.
Rondini EA, Duniec-Dmuchowski Z, Cukovic D, Dombkowski AA, Kocarek TA. Differential Regulation of Gene Expression by Cholesterol Biosynthesis Inhibitors That Reduce (Pravastatin) or Enhance (Squalestatin 1) Nonsterol Isoprenoid Levels in Primary Cultured Mouse and Rat Hepatocytes. J Pharmacol Exp Ther. 2016;358:216-29.
Irish JC, Mills JN, Turner-Ivey B, Wilson RC, Guest ST, Rutkovsky A, Dombkowski A, Kappler CS, Hardiman G, Ethier SP. Amplification of WHSC1L1 regulates expression and estrogen-independent activation of ERα in SUM-44 breast cancer cells and is associated with ERα over-expression in breast cancer. Mol Oncol. 2016;10:850-65.
Dombkowski AA, Batista CE, Cukovic D, Carruthers NJ, Ranganathan R, Shukla U, Stemmer PM, Chugani HT, Chugani DC. Cortical Tubers: Windows into Dysregulation of Epilepsy Risk and Synaptic Signaling Genes by MicroRNAs. Cereb Cortex. 2016;26:1059-71.
Chen L, Martino V, Dombkowski A, Williams T, West-Mays J, Gage PJ. AP-2β Is a Downstream Effector of PITX2 Required to Specify Endothelium and Establish Angiogenic Privilege During Corneal Development. Invest Ophthalmol Vis Sci. 2016;57:1072-81.
Barrett KG, Fang H, Cukovic D, Dombkowski AA, Kocarek TA, Runge-Morris M. Upregulation of UGT2B4 Expression by 3'-Phosphoadenosine-5'-Phosphosulfate Synthase Knockdown: Implications for Coordinated Control of Bile Acid Conjugation. Drug Metab Dispos. 2015;43:1061-70.
Caruso JA, Stemmer PM, Dombkowski A, Caruthers NJ, Gill R, Rosenspire AJ. A systems toxicology approach identifies Lyn as a key signaling phosphoprotein modulated by mercury in a B lymphocyte cell model. Toxicol Appl Pharmacol. 2014;276:47-54.
Caruthers NJ, Stemmer PM, Shin N, Dombkowski A, Caruso JA, Gill R, Rosenspire A. Mercury alters B-cell protein phosphorylation profiles. J Proteome Res. 2014;13:496-505.
Dombkowski AA, Sultana KZ, Craig DB. Protein disulfide engineering. FEBS Lett. 2014;588:206-12.
Education and Training:
Ph.D. (2001) University of Michigan, Ann Arbor, MI Pharmaceutical Chemistry (Computational)
M.Sc. (1999) University of Michigan, Ann Arbor, MI Biophysics
B.S. (1995) University of Houston, Houston, TX Biochemical and Biophysical Sciences
Cancer Biology Courses Taught:
CB7300 Functional Genomics and Bioinformatics