Bina Joe, Ph.D., FAHA
Professor, Program in Physiological Genomics
The Program in Physiological Genomics of the Department of Physiology and Pharmacology is focused on understanding the genetic components of pathophysiological conditions of the cardiovascular, renal and autoimmune systems. The most prominent of all complex traits investigated in the Joe laboratory is blood pressure regulation. 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 whole genome systems biology approaches. We have identified at least 16 different genomic regions that harbor quantitative trait loci (QTLs) for hypertension in rats and successfully mapped several of these regions to unparalleled resolutions of a few kilobases. Positional cloning projects have progressed to the identification of multiple novel genes as prominent BP QTLs in rats. Methodical mechanistic studies spanning from molecular to whole-organism physiology/pathophysiology are underway to determine the functional significance of the novel BP QTLs identified. Genetic-engineering technologies such as the application of zinc-finger nuclease-based targeted gene disruption for creation of 'knock-out' and 'knock-in' rat models are also strategies integrated into our research for validation of the positionally cloned causal genetic biomarkers of blood pressure regulation. Finally, the translational significance of our work is exemplified by the validation of the positionally cloned rat genes as being associated or linked with human hypertension.
Awards and Commendations:
- University of Toledo Change team leader for Institutions Developing Excellence in Academic Leadership (2011-2012)
- American Society of Hypertension Young Scholar Award, 2010
- Fellow of the American Heart Association, 2010
- Fogarty visiting scientist fellowship award, NIH, Bethesda, USA, 1997
- Nationally competitive Senior Research Scholarship award, Council for Scientific and Industrial Research, India, 1993
- Nationally competitive Junior Research Scholarship award, Council for Scientific and Industrial Research, India, 1989
- National Merit Scholarship award, India, 1988-1990
- Scientist, ASTRA, Bangalore, India, 1996-1997
- Research Assistant Professor, Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo, OH, Apr 2001- Mar 2004
- Assistant Professor, Department of Physiology, Pharmacology, Metabolism, and Cardiovascular Sciences, University of Toledo College of Medicine, Health Science Campus, April 2004-June 2007
- Associate Professor (Awarded Tenure 2008), Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, July 2007-2010
- Professor, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Health Science Campus, 2011-
- Scientific Advisor, Rat Genome Database (http://rgd.mcw.edu/), 2003-present
- Refined Mapping of Blood Pressure quantitative trait loci using congenic strains developed from two genetically hypertensive rat models. Kumarasamy S, Gopalakrishnan K, Toland EJ, Yerga-Woolwine S, Farms P, Morgan EE and Joe B. Hypertens. Res. (In press), 2011
- Impairment of Na/K-ATPase Signaling in Renal Proximal Tubule Contributes to Dahl Salt-Sensitive Hypertension. Liu J, Yan Y, Liu L, Xie Z, Malhotra D, Joe B and Shapiro JI, J. Biol. Chem. 286: 22806-22813, 2011.
- Genetic influences on survival time after severe hemorrhage in inbred rat strains. Klemcke HG, Joe B, Calderon ML, Rose R, Oh T, Aden J and Ryan KL. Physiol Genomics Current Genomics (In press), 2011.
- Augmented rififylin is a risk factor linked to aberrant cardiomyocyte function, short QT-interval and hypertension. Gopalakrishnan K, Morgan EE, Yerga-Woolwine S, Farms P, Kumarasamy S, Kalinoski A, Liu X, Wu J, Liu L, Joe B. Hypertension. 57: 764-771, 2011.
- Defining a rat blood pressure quantitative trait locus to a <81.8kb congenic segment: comprehensive sequencing and renal transcriptome analysis. Gopalakrishnan K, Saikumar J, Peters CG, Kumarasamy S, Farms P, Yerga-Woolwine S, Toland EJ, Schnackel W, Giovannucci DR, Joe B. Physiol. Genomics. 42A: 153-161, 2010. (Accompanied by an Editorial Commentary)
- Mitochondrial Polymorphisms in Rat Genetic Models of Hypertension. Kumarasamy S, Gopalakrishnan K, Shafton A, Nixon J, Thangavel J, Farms P, Joe B. Mamm Genome 21(5-6): 299-306, 2010.
- Joe, B., Saad, Y., Lee, N.H., Frank, B.C., Achinike, O.H., Luu, T.V., Gopalakrishnan, K., Toland, E.J., Farms, P., Yerga-Woolwine, S., Manickavasagam, E., Rapp, J.P., Garrett, M.R., Coe, D., Apte, S.S., Rankinen, T., Pérusse, L., Ehret, G.B., Ganesh, S.K., Cooper, R.S., O'Connor, A., Rice, T., Weder, A.B., Chakravarti, A., Rao, D.C., Bouchard, C.. Positional identification of variants of Adamts16 linked to inherited hypertension. Human Molecular Genetics. 18(15):2825-38, 2009.
- Cicila, G.T., Morgan, E.E., Lee, S.J., Farms, P., Yerga-Woolwine, S., Toland, E.J., Ramdath, R.S., Gopalakrishnan, K., Bohman, K., Nestor-Kalinoski, A.L., Chuder, S.A. and Joe, B. Epistatic Genetic Determination of Blood Pressure and Mortality in a Salt-Sensitivie Hypertension Model. Hypertension 53(4) 725-732, 2009.
- Toland, E.J., Yerga-Woolwine, S., Farms, P., Cicila, G.T., Saad, Y., and Joe, B. Blood pressure and proteinuria effects of multiple quantitative trait loci on rat chromosome 9 that differentiate the spontaneously hypertensive rat from the Dahl salt-sensitive rat. Journal of Hypertension 26(11):2134-2141, 2008.
- 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, 19(3): 209-218, 2008.
- 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.