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Center for Human Genomics at Wake Forest University School of Medicine

Gregory A. Hawkins
Associate Professor of Internal Medicine
Section on Pulmonary, Critical Care, Allergy and Immunologic
Director DNA Sequencing Laboratory
Center for Human Genomics

B.A., 1984 (Chemistry) University of North Carolina - Chapel Hill
Ph.D., 1990 (Biochemistry) University of Maryland - College Park

Office (336) 713-7511
Lab (336) 713-7141
ghawkins@wfubmc.edu

Research Interests

My primary research interests focus on pharmacogenetics related to asthma therapy, primarily in the corticosteroid and beta-2 agonist pathways.  Currently, we are investigating the potential genetic contribution of genes that encode components of the glucocorticoid receptor hetero-complex towards variations in corticosteroid response.  Two genes have become of increased interest: STIP1, which encodes the heat shock organizing protein, and FKBP4, which encodes the immunophilin FKBP52.  In a recent publication, we reported that genetic and haplotypic variations in STIP1 correlate not only with levels of lung function as measured by FEV1, but also correlate with response to corticosteroid therapy (Hawkins et al. 2009 J. Allergy Clin. Immun. 123(6):1376-83).  We have recently genotyped STIP1 in two additional asthma populations, and have continued to observe strong associations with measures of lung function.  One of these populations, the NHLBI sponsored Severe Asthma Research Program (SARP), contains a high portion of severe asthmatics that consistently have poor responses to corticosteroid therapy.

 

As second key research interest is the pharmacogenetics of beta-2 agonist therapy.  Our laboratory has published the most detailed DNA sequence analysis of the gene encoding the target of beta agonists, the beta-2 receptor (ADRB2) (Hawkins et al. 2006 Am. J. Resp. Care Crit. Med 174:1101-1109).  Our results showed a high degree of genetic and haplotypic variation in addition to the identification of rare, potentially function genetic variations.  We are now focusing on the epigenetic regulation of ADRB2 expression by comparing patterns of DNA methylation in ADRB2 with gene expression and cellular response to beta agonist exposure.

 

Finally, as Director of the DNA Sequencing Laboratory in the Center for Human Genomics, I collaborate with numerous investigators across the Medical School to provide high-throughput DNA sequencing and analysis.

Selected Publications (2004-2009)

Koppelman GH, Meyers DA, Howard TD, Zheng SL, Hawkins GA, Ampleford EJ, Xu J, Koning H, Bruinenberg M, Nolte IM, te Meerman GJ, van Diemen CC, Boezen HM, Timens W, Whittaker PA, Stine OC, Holloway JW, Holgate, ST, Graves PE, Martinez FD, van Oosterhout A, Bleecker ER, Postma DS  Asthma Positional Cloning:  PCDH1, a Susceptibility Gene for Bronchial Hyperresponsiveness (2009) Am. J. Resp. Care Crit. Med (Submitted)

 

Sadeghnejad A, Ohar JA, Zheng SL, Sterling DA, Hawkins GA, Meyers DA, Bleecker ER  ADAM33 Polymorphisms are Associated with COPD and Lung Function in Long-Term Tobacco Smokers (2009) Respiratory Research 10:21.

 

Hawkins GA, Lazarus R, Smith RS, Tantisira KG, Meyers DA, Weiss ST, Bleecker ER Glucocorticoid Receptor Hetero-Complex Gene STIP1 Is Associated with Improved Lung Function in Asthmatics Treated with Inhaled Corticosteroids (2009) J. Allergy Clin. Immun. 123(6):1376-83.

 

El Gazzar M, Yoza BK, Hu JY, Chen X, Hawkins GA, McCall CE  The Heterochromatin protein 1 links histone and DNA methylation to TNFα  transcription silencing during endotoxin tolerance  (2008) J. Biol. Chem. 283(47):32198-208.

 

Litonjua AA, Tantisira KG, Schneiter K, Lasky-Su J, Lazarus R, Richter B, Klanderman B,  Lima JL, Hanrahan J, Liggett S, Hawkins GA, Meyers DA, Bleecker ER, Lange C, Weiss ST Arginase 1 is a novel bronchodilator response gene: screening and replication in four asthma cohorts (2008)  Am. J. Resp. Care Crit. Med 178(7):688-94

 

Orlowski, RJ, O’Rourke, SS, Olorenshaw, I, Hawkins GA, Maas, S, Laxminarayana D  Altered Editing in Cyclic Nucleotide Phosphodiesterase 8A1 (PDE8A1) Gene Transcripts of Systemic Lupus Erythematosus (SLE) T Lymphocytes (2008) Immunology 125:1-12.

 

Hawkins GA, Weiss ST, Bleecker ER  The Clinical Consequences of Beta-2 Receptor Polymorphisms in Asthma (2008) Pharmacogenomics 9(3):349-358.

 

Blish, KR, Willingham MC, Du W, Birse C, Brown JC, Hawkins GA, Garvin AJ, Agostino RBD,Torti FM, Torti SV.  Differential Expression of the Bone Morphogenic Protein Antagonist BARC in Renal Cancers (2008) Mol. Biol. Cell 19:457-464.

 

Hawkins GA, Meyers DA, Bleecker ER, Pack AI Identification of Coding Variants in the Human Circadian Rhythm Genes PER1, PER2, PER3, CLOCK, ARNTL, CRY1, CRY2, and TIMELESS in a Multi-National Screening Population (2008) DNA Sequence 19:44-49.

 

Panebra A, Schwarb MR, Swift SM, Hawkins GA, Liggett SB  Variable Length Poly-C Tract Polymorphisms of the b2-adrenergic Receptor 3’UTR Alter Expression and Agonist Regulation  (2008) American Journal of Physiology- Lung  294:L190-L195.

 

Ortega VE, Hawkins GA, Peters SP, Bleecker ER  Pharmacogenetics of the Beta-2 Receptor Gene (2007) Immunology and Allergy Clinics of North America  27:665-84.

 

Hawkins GA, Ortega V, Bleecker ER  Detailed Sequence Analysis of the Beta-2 Receptor Gene in Caucasians and African Americans.  (2007) Allergy & Clinical Immunology International :  J. World Allergy Org, Supplement 2:277-284.

 

Mallakin A, Matise LA, Taneja P, Frazier DP, Chaudohry M, Allen S, Clark J, Hawkins GA, Willingham MC, and Inoue K   Critical role of DMP1 in human and murine lung cancer (2007) Cancer Cell 12:381-394.

 

Smith R, Meyers DA, Wenzel SE, Peters SP, Bleecker ER, Hawkins GA  Sequence Analysis of HSPA1A and HSPA1B in a Multi-Racial Asthma Case and Control Screening Panel  (2007) DNA Sequence 18(1):47-53.

 

Wenzel SE, Balzar S, Ampleford EJ, Hawkins GA, Busse WW, Calhoun WJ, Castro M, Chung KF. Erzurum S, Gaston B, Israel E, Teague EG, Meyers DA, Bleecker ER for the NHLBI Serve Asthma Research Program   Mutations in the IL-4Ra Receptor are associated with Severe Asthma Exacerbations, Tissue Mast Cells/IgE Expression and Racial Background (2007) Am. J. Resp. Care Crit. Med 175:570-576.

 

Hawkins GA, Tantisira KG, Myers DA, Ampleford EJ, Moore WC, Peters SP, Liggett SB, Weiss ST, Bleecker ER.  Sequence and Haplotype Analysis of the ADRb2 in Multi-Ethnic Asthma Case/Control Subjects (2006) Am. J. Resp. Care Crit. Med 174: 1101-1109.

 

Hastie AT, Wu M, Foster GC, Hawkins GA, Batra V, Rybinski KA, Cirelli R, Zangrilli JG, Peters SP  Alterations in vasodilator-stimulated phosphoprotein (VASP)phosphorylation: associations with asthmatic phenotype, airway inflammation and beta2-agonist use (2006) Respiratory Research 15;7(1):25.

 

Hawkins GA, Weiss ST, Bleecker ER.  Pharmacogenomics in Asthma (2005) Immunology and Allergy Clinics of North America 25(4):723-42.48.

 

Engeler Dusel JA, Burdon KP, Hicks PJ, Hawkins GA, Bowden DW, Freedman BI  Identification of NPHS2 gene mutations in African Americans with hypertension associated End-Stage Renal Disease (2005) Kidney International 68:256-262.

 

Basehore MJ, Howard TD, Lange LA, Moore WC, Hawkins GA, Marshik PL, Harkins MS, Meyers DA, Bleecker ER A comprehensive evaluation of IL4 variants in ethnically diverse populations: Association of total serum IgE levels and asthma in white subjects (2004) J Allergy Clin Immunol. 114(1):80-87.

 

Hawkins GA, Amelung PJ, Smith R, Jongepier H, Howard TD, Koppelman GH, Meyers DM, Bleecker ER, Postma DS Identification of Polymorphisms in the Human Glucocorticoid Receptor Gene (NR3C1) in a Multi-Racial Asthma Case and Control Screening Panel  (2004) DNA Sequence 15(3):167-173.

 

Hawkins GA, Isaacs SD, Wiley KE, Chang B-L, Ewing CM, Carpten JD, Bleecker ER, Walsh PC, Trent JM, Isaacs WB, Xu J Mutation Analysis of PinX1 Polymorphisms in Hereditary Prostate Cancer (2004) The Prostate 60(4):298-302.

 

Register TC, Burdon KP, Lenchik L, Bowden, DW, Hawkins GA, Nicklas BJ, Lohman K, Hsu F-C, Langefeld CD, Carr JJ,  Variability of Serum Soluble Intercellular Adhesion Molecule-1 Measurements Attributable to a Common Polymorphism (2004) Clinical Chemistry 50(11):2185-2187.

 

Jones DW, Russell G, Alford SL, Hawkins GA,  Bowden DW, Mumford AD  Severe prekallikrein deficiency associated with homozygosity for an Arg94Stop nonsense mutation. (2004) British J. Haematology 127(2):220-3.