Physiology and Pharmacology : Bina Joe, Ph.D.

Associate Professor Phone: (419) 383-4415 Fax: (419) 383-2871 Email: bina.joe@utoledo.edu

Genetics of hypertension research

Physiological Genomics Laboratory

Training:

• B.S., 1988, Biochemistry, Botany and Zoology, University of Mysore, Mysore, Karnataka, India
• M.S., 1990, Biochemistry, University of Mysore, Mysore, Karnataka, India
• Ph.D., 1996, Biochemistry, University of Mysore, Mysore, Karnataka, India

Post-doctoral Fellowships:

• Center for Reproductive Biology and Molecular Endocrinology, Indian Institute of Science, Bangalore, India, 1995-1996
• National Institute of Arthritis, Musculoskeletal and Skin Diseaseas, National Institutes of Health, Bethesda, MD, USA, 1997-2001

Appointments:

• Scientist, ASTRA, Bangalore, India, 1996-1997
• Assistant Professor (Research Track), Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo, OH, Apr 2001- Mar 2004
• Assistant Professor (Tenure Track), Department of Physiology, Pharmacology, Metabolism, and Cardiovascular Sciences, University of Toledo College of Medicine, Health Science Campus, April 2004-June 2007
• Associate Professor (Tenure Track), Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, July 2007-present
• Scientific Advisor, Rat Genome Database (http://rgd.mcw.edu/), 2003-present

Awards and Commendations:

• National Merit Scholarship award, India, 1988-1990
• Nationally competitive Junior Research Scholarship award, Council for Scientific and Industrial Research, India, 1989
• Nationally competitive Senior Research Scholarship award, Council for Scientific and Industrial Research, India, 1993
• Fogarty visiting scientist fellowship award, NIH, Bethesda, USA, 1997

Research Interest:

Dr. Joe's laboratory, the Physiological Genomics Laboratory, is focused on understanding the genetic component of blood pressure regulation using hypertensive rat models. Rat models serve as valuable alternatives to human studies for the identification and characterization of genetic factors/genes. The main strategy is to identify the disease causative genetic factor/gene based on its location on the rat genome by linkage analysis and substitution mapping and/or gene expression and protein expression profiling using custom oligonucleotide arrays, rat genome microarrays and rat proteomics. To this end, we have identified at least 16 different genomic regions that harbor quantitative trait loci (QTLs) for hypertension in rats. All but one of these QTLs remain unidentified. Fine-mapping of several regions to less than 1Mb segments of the rat genome has been achieved. Current efforts are underway to positionally clone the underlying QTL effectors. The expectation is to be able to translate our observations in rat models to disease causative mechanisms in humans.

Representative Publications:

• Toland, E.J., Saad, Y., Yerga-Woolwine, S., Ummel, S., Farms, P., Ramdath, R., Frank, B.C., Lee, N.H., and Joe, B. Closely linked non-additive blood pressure quantitative trait loci. Mammalian Genome, 2008 Mar 7; [Epub ahead of print].
• Saad, Y., Toland, E.J., Yerga-Woolwine, S., Farms, P., and Joe, B. Congenic mapping of a blood pressure QTL region on rat chromosome 10 using the Dahl salt-sensitive rat with introgressed alleles from the Milan normotensive strain. Mammalian Genome Feb; 19 (2):85-91, 2008, (cover).
• Saad, Y., Yerga-Woolwine, S., Saikumar, J., Farms, P., Manickavasagam, E., Toland, E., and Joe, B. Congenic interval mapping of RNO10 reveals a complex cluster of closely-linked genetic determinants of blood pressure. Hypertension 50:891-898, 2007.
• Lee, N.H., Haas, B.J., Letwin, N.E., Frank, B.C., Luu, T.V., Sun, C., Yerga-Woolwine, S., Farms, P., Manickavasagam, E., and Joe, B. Cross-talk of expression quantitative trait loci within two interacting blood pressure quantitative trait loci. Hypertension 50(6):1126-1133, 2007.
• Klemcke, H.G., Baer, D.G., Pankratz, V.S., Cox, A., Cortez, D.S., Garrett, M.R., Joe, B., and Ryan, K.L. Is survival time after hemorrhage a heritable, quantitative trait? An initial assessment. Shock Nov, 2007.
• Saad, Y., Garrett, M.R., Manickavasagam, E., Yerga-Woolwine, S., Farms, P., Radecki, T., and Joe B. Fine-mapping and comprehensive transcript analysis reveals nonsynonymous variants within a novel 1.17 Mb Blood Pressure QTL region. Genomics 89: 343-353, 2007.
• Lee, S.J., Liu, J., Wescott, A.M., Veith, J.A., DeRaedt, S.J., Yang, S., Joe, B., and Cicila, G.T. Substitution mapping in Dahl rats identifies two distinct blood pressure quantitative trait loci within 1.12Mb and 1.25Mb intervals on chromosome 3. Genetics 174:2203-2213, 2006.
• Garrett, M.R. and Joe, B. Genetic studies of inherited hypertension in the rat. 2006. Handbook of Hypertension 23: Dominiczak and Connell: Genetics of Hypertension..
• Garrett, M.R., Joe, B., and Yerga-Woolwine, S. Genetic Linkage of Urinary Albumin Excretion in Dahl Salt-Sensitive Rats: Influence of Dietary Salt and Confirmation using Congenic Strains. Physiological Genomics 25: 39-49, 2006.
  Garrett, M.R., Meng, H., Rapp, J.P., and Joe B. Localization of a blood pressure QTL to a 117kb region on the rat genome: Substitution mapping and gene expression analysis. Hypertension 45:1-9, 2005.
• Joe B., Verratti, K., Letwin, N.E., Garrett, M.R., Lee, N.H., and Rapp, J.P. Transcriptional profiling with a blood pressure QTL interval-specific oligonucleotide array. Physiological Genomics 23: 318-326, 2005.
• Joe B. and Garrett M.R. Substitution Mapping: Using congenic strains to detect genes controlling blood pressure. 2005. Cardiovascular Genomics, Humana Press, Inc; Raizada MK, Paton JFR, Kasparov S and Katovich MJ (Editors).
• Joe B., Garrett, M.R., Dene, H., and Rapp, J.P. 2003. Substitution mapping of a blood pressure QTL to a 2.73Mb region on rat chromosome 1. J Hypertension 21:2077-2084, 2003. # Article accompanied by an Editorial commentary.
• Joe B., M. R. Garrett, H. Dene, E. F. Remmers, H. Meng. Genetic susceptibility to carrageenan-induced innate inflammatory response in inbred strains of rats. Eur J Immunogenetics 30:243-247, 2003.
• Garrett, M.R., Joe, B., Dene, H., and Rapp, J. P. Identification of blood pressure QTL that differentiate two hypertensive strains. J Hypertension 20:2399-2406, 2002.
• Joe B. The quest for arthritis causative genes in the rat. (Invited review); Physiological Genomics 27:1-11, 2006.
• Brenner, M,, Meng, H., Nuriza, C., Yarlett, B.S., Joe, B., Griffiths, M.M., Remmers, E.F., Wilder, R.L., and Gulko, P.G.  The non-MHC quantitative trait locus Cia5 contains two major arthritis genes that differentially regulate disease severity, pannus formation and joint damage in collagen-and pristane-induced arthritis. J. Immunol. 174: 7894-7903, 2005.
• Joe B., G. W. Cannon, M. M. Griffiths, D. E. Dobbins, P. S. Gulko, R. L. Wilder, E. F. Remmers. Evaluation of mycobacterial adjuvant-induced arthritis (Mbt-AIA) severity QTLs isolated in mono-congenic and poly-congenic rats: Identification of a new regulatory locus on rat chromosome 10, and evidence that Mbt-AIA loci overlap rheumatoid arthritis susceptibility loci. Arthritis Rheum 46:1075-1085, 2002.
• Joe, B., Remmers, E.F., Dobbins, D.E., Salstrom, J.L., Furuya, T., Dracheva, S., Gulko, P.S., Cannon, G.W., Griffiths, M.M., and Wilder R.L.  Genetic dissection of collagen-induced arthritis in Chromosome 10 quantitative trait locus speed congenic rats: evidence for more than one regulatory locus and sex influences. Immunogenetics 51: 930-944, 2000.
• Dobbins, D.E., Joe, B., Hashiramoto, A., Salstrom, J.L., Dracheva, S., Ge, L., Wilder, R.L., and Remmers, E.F.  Localization of the mutation responsible for osteopetrosis in the op rat to a 1.5cM genetic interval on rat chromosome 10: Identification of positional candidate genes by radiation hybrid mapping. J Bone and Min Res 17:1761-1767, 2002.
• Remmers, E.F., Joe, B., Griffiths, M.M., Dobbins, D.E., Dracheva, S., Hashiramoto, A., Furuya, T., Salstrom, J.L., Wang, J., Gulko, P.S., Cannon, G.W.,  and Wilder, R.L.  Modulation of multiple experimental arthritis models by collagen-induced arthritis quantitative trait loci isolated in congenic rat lines: different effects of non-major histocompatibility complex quantitative trait loci in males and females. Arthritis Rheum 46: 2225-2234, 2002.
• Griffiths, M.M., Wang, J., Joe, B., Dracheva, S.V., Kawahito, Y., Shepard, J.S., Reese, V.R., McCall-Vining, S., Hashiramoto, A., Cannon, G.W., Remmers, E.F., and Wilder, R.L.  Identification of four new QTL regulating arthritis severity and one new QTL regulating autoantibody production in rats with collagen-induced arthritis. Arthritis Rheum 43: 1278-1289, 2000.
• Furuya, T., Salstrom, J.L., McCall-Vining, S., Cannon, G.W., Joe, B., Remmers, E.F., Griffiths, M.M., and Wilder, R.L.  Genetic dissection of a rat model for rheumatoid arthritis: significant gender influences on autosomal modifier loci. Hum Mol Genet 9: 2241-2250, 2000.
• Furuya, T., Salstrom, J.L., Joe, B., Hashiramoto, A., Dobbins, D.E., Wilder, R.L., and Remmers, E.F.  Polymorphisms of the tumor necrosis factor receptor type 1 locus among autoimmune susceptible and resistant inbred rat strains. Immunogenetics 53: 427-429, 2001.
• Furuya, T, Joe, B., Salstrom, J.L., Hashiramoto, A., Dobbins, D.E., Wilder, R.L., Remmers, E.F.  Polymorphisms of the tumor necrosis factor alpha locus among autoimmune disease susceptible and resistant inbred rat strains. Genes and Immunity 2: 229-232, 2001.