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John L. Hartman, MD

Associate Professor
Genetics
KAUL 702 Zip 0024
Birmingham, AL 34294-1250
Phone: 205-996-4195
E-mail: jhartman@uab.edu
Website


Biographical Sketch

John Hartman received a B.S. in Zoology from Duke University in 1989, and an M.D. from UAB in 1995. He completed Internal Medicine Residency and Hematology Fellowship at the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, WA from 1997-2001. Past research experience has been with Max Cooper (UAB, Immunology), George Philips (Duke, Hematology), Eric Sorshcer (UAB, Cystic Fibrosis), John Northup (NIH, G-protein Signaling), and Lee Hartwell (Fred Hutchinson Cancer Research Center, Yeast Genetics). Past awards include a Howard Hughes Medical Institute (HHMI) Research Fellowship for Medical Students, HHMI Research Fellowship for Physician-Scientists, NIH K08 Career Development Award, HHMI Early Career Award for Physician-Scientists, and American Cancer Society Research Scholar Grant.

Research/Clinical Interest

Quantitative analysis of genotype-phenotype interaction networks in yeast models of human disease
Biological systems are robust, having the capacity to maintain relatively stable phenotypic outputs over a range of perturbing genetic and environmental inputs. Genetic buffering refers to gene activities within a cell that confer phenotypic stability in a particular context. Genetic interactions, defined whenever the phenotype resulting from a chemical or genetic perturbation is dependent upon a particular gene, reveal buffering; examples being chemical sensitivity or synthetic lethality. Research in the lab is focused on global, quantitative analysis of genetic interactions, and understanding how the structure of interaction networks reflects the global organization of gene circuitry that provides cellular robustness. To measure gene interaction globally, we perturb an array of ~5000 isogenic yeast deletion strains, and use cell proliferation as a phenotypic readout to quantify the interacting effects between the perturbation and deletion at each locus. By varying the type and intensity of perturbation, the resulting selectivity and strengths of interaction are determined, revealing the relative buffering specificity of each gene. Using gene annotation and other bioinformatics resources to analyze the quantitative patterns of gene interaction, testable hypotheses are generated to further understand the molecular basis of the observed interaction networks. Genes that interact (exacerbate or compensate) with a known genetic or environmental disease-susceptibility factor can act as disease modifiers, contributing to complex disease traits. Systematic, comprehensive, quantitative understanding of how genetic buffering and cellular robustness are achieved in the highly tractable yeast model system is a strategy for understanding complex genotype-phenotype relationships that may exist generally for eukaryotic cells. The Hartman laboratory has developed novel methodologies for the type of global, quantitative analysis of genetic interactions described above, and these are being applied to understand robustness against perturbations that contribute to cancer and other diseases. Dr. Hartman has GBS affiliations with: Genetics & Genomic Sciences (GGS) Cell, Molecular, & Developmental Biology (CMDB) Biochemistry & Structural Biology (BSB)

Selected Publications

  1. Hartman, J.L. and Northup, J.K. (1996). Functional reconstitution in situ of 5-hydroxytryptamine2c (5HT2c) receptors with aq and inverse agonism of 5HT2c receptor antagonists. J. Biol. Chem. 271: 22591-22597. 8798428 
  2. Mai D, Jones J, Rodgers JW, Hartman JL, Kutsch O, Steyn AJ. A Screen to Identify Small Molecule Inhibitors of Protein-Protein Interactions in Mycobacteria. Assay Drug Dev Technol 2011. 21281130 
  3. Gao S, Hartman IV JL, Carter JL, Hessner MJ, Wang X. Global analysis of phase locking in gene expression during cell cycle: the potential in network modeling. BMC Syst Biol 2010;4:167. 21129191 
  4. Guo, J., Tian, D., McKinney, B.A., and Hartman, J.L. (2010). Recursive expectation-maximization clustering: a method for identifying buffering mechanisms composed of phenomic modules. Chaos 20, 026103. 20590332 
  5. Copic A, Dorrington M, Pagant S, Barry J, Lee MC, Singh I, Hartman IV JL, Miller EA: Genomewide analysis reveals novel pathways affecting endoplasmic reticulum homeostasis, protein modification and quality control. Genetics 2009, 182(3):757-769. 19433630 
  6. Singh I, Pass R, Togay SO, Rodgers JW, Hartman IV JL: Stringent Mating-Type-Regulated Auxotrophy Increases the Accuracy of Systematic Genetic Interaction Screens with Saccharomyces cerevisiae Mutant Arrays. Genetics 2009, 181(1):289-300. 18957706 
  7. Mani, R., St Onge, R.P., Hartman IV, J.L., Giaever, G. & Roth, F.P. (2008) Defining genetic interaction. Proc Natl Acad Sci U S A. 18305163 
  8. Hartman IV JL (2007). Buffering of deoxyribonucleotide pool homeostasis by threonine metabolism. Proc Natl Acad Sci U S A. 17606896 
  9. Jones J, Rodgers J, Heil M, May J, White L, Maddry JA, Fletcher TM, Shaw GM, Hartman JL, Kutsch O: High throughput drug screening for human immunodeficiency virus type 1 reactivating compounds. Assay Drug Dev Technol 2007, 5(2):181-190. 17477827 
  10. Shah, N.A,, Laws, R.J., Wardman, B, Zhao, L.P., Hartman IV, J.L. (2007) Accurate, precise modeling of cell proliferation kinetics from time-lapse imaging and automated image analysis of agar yeast culture arrays. BMC Systems Biology 2007, 1:3. 17408510 
  11. Hartman IV, J.L. and Nic Tippery (2004) Systematic quantification of gene interactions by phenotypic array analysis. Genome Biology 5(7):R49. 15239834 
  12. Hartman, J., Huang Z., Rado, T., Peng, S., Jilling T., Muccio, D.D. and Sorscher, E.J. (1992). Recombinant synthesis, purification and nucleotide binding characteristics of the first nucleotide binding domain of the cystic fibrosis gene product. J. Biol. Chem. 267: 6455-6458. 1372605 
  13. Hartman IV, J.L., Garvik, B., and Hartwell, L. (2001) Principles for the buffering of genetic variation. Science 291(5506):1001-4. 11232561