The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

 Manuel Gonzalez-Garay, Ph.D.

Manuel Gonzalez-Garay, Ph.D.

Assistant Professor, Center for Molecular Imaging

Manuel.L.GonzalezGaray@uth.tmc.edu

713-500-3032

My program is motivated by the unprecedented achievement in which the entire human genome was sequenced to near completion in 2000 by hundred of scientists worldwide using sequence technology that was develop in the early 1970s by Frederick Sanger. It took over 10 years and over $3 billion to sequence for first time the human genome. The development of massively parallel DNA sequencing technologies (Next Generation Sequencing, NGS) in 2005 brought a paradigm shift to biomedical research. NGS made it possible to sequence a human genome for few thousand dollars in few weeks, transferring the challenge of sequencing a genome to the bioinformatics analysis and interpretation of the information.

I foresee a day in the near future when getting your genome sequenced and interpreted will be standard practice. To get to this point, we need to develop tools to analyze the whole genome sequence, interpret the information and detect markers that will allow physicians to develop personalized treatment for every patient. My group recently published a proof of concept study of the usability of next generation sequencing (NGS) for genetic screening of healthy adults. For our study we specifically selected a group of middle age individuals with abundant medical records and strongly motivated to improve their health. There are many conditions that are detected at middle age for example cardiovascular disorders, eye disorders like cataracts, hearing loss, metabolic disorders and many types of cancers. Many of our volunteers already suffered and survived many of these maladies but they lack of a molecular explanation for the disorder.  Our findings were substantial, we linked personal disease histories with causative disease genes in 18 volunteers, in addition we identified risk alleles for breast, ovarian, colon, prostate cancer in many volunteers some of them with previous cancer diagnosis or/and strong family history.

Another main focus of my laboratory is to detect and associate genetic markers (variations) with rare genetic disorders.  We recently published an important discovery of a new association between the gene MAGEL2, autism and Prader-Willi Syndrome.  We also have been able to demonstrate that mutations in RASA1 gene are associated with lymphatic abnormalities in mouse and humans. My group currently has multiple collaborations with renowned scientists at UTHealth, who work in multiple areas like Drs. Eva Sevick (Lymphedema), Peter Doris (High blood pressure and kidney function), Brian Davis (Stem Cell), Hope Northrup (Pediatric disorders), Michael Lorenz (Candida albicans),  etc.  In addition, we are working with several other scientists from other institutions to identify genetic markers associated with familial panic disorders, Dercum's disease, Adiposis dolorosa and Madelung’s disease.

Research Project:

  • Genome and Bioinformatics Analysis of patients with Lymphedema.
  • Personalized medicine using next generation sequencing: The CEO Genome Project.
  • Detection of markers for sudden death syndrome in a population from Venezuela. Collaborator of Dr. Rosalva Rodríguez, Instituto Venezolano de Investigaciones Cientificas.
  • Identification of genetic markers for Panic disorders in Monterrey, N. L. Mexico. Collaborator of Dr. Augusto Rojas-Martinez, Universidad Autonoma de Nuevo Leon.
  • Virulence factor identification by comparative transcriptomics in Candida species. Collaborator of Michael Lorenz, Ph.D. UTHealth.
  • Hypertensive Renal Injury. Collaborator of Peter Doris, Ph.D. UTHealth.
  • Dercum's disease, Adiposis dolorosa, Madelung's disease. Collaborator of Karen L Herbst, M.D. UC San Diego.

       

Selected peer-reviewed publications (in chronological order).

  • Gonzalez-Garay, M. L., and F. Cabral.  1995.  Overexpression of an epitope-tagged beta-tubulin in Chinese hamster ovary cells causes an increase in endogenous alpha-tubulin synthesis.  Cell Motil Cytoskeleton 31:259-272. PMID: 7553913
  • Gonzalez-Garay, M. L., and F. Cabral. 1996. Alpha-Tubulin Limits Its Own Synthesis: Evidence for a Mechanism Involving Translational Repression. J Cell Biol. 135:1525-34. PMID: 8978820
  • Gonzalez-Garay, M. L., Chang, L., Blade, K., Menick, D. R., and Cabral, F. (1999). A beta-tubulin leucine cluster involved in microtubule assembly and paclitaxel resistance. J Biol Chem 274: 23875-82. PMID: 10446152
  • Barlow SB, Gonzalez-Garay M.L, Cabral F. 2002. Paclitaxel-dependent mutants have severely reduced microtubule assembly and reduced tubulin synthesis. J Cell Sci. 115:3469-3478. PMID: 12154077
  • The Rat Genome Sequencing Project Consortium.  2004. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428:493-521. PMID: 15057822
  • The Human Chromosome 12 Group.  2006. The finished DNA sequence of human chromosome 12. Nature 440:346-51. PMID: 16541075
  • The Human Chromosome 3 Group.  2006. The DNA sequence, annotation and analysis of human chromosome 3. Nature 440:1194-8. PMID: 16641997
  • Sea Urchin Genome Sequencing Consortium.  2006. The genome of the sea urchin Strongylocentrotus purpuratus. Science 314:941-52. PMID: 17095691
  • Comprehensive genomic characterization defines human glioblastoma genes and core pathways. 2008. Nature 455:1061-1068. PMID: 18772890
  • Somatic mutations affect key pathways in lung adenocarcinoma.  2008. Nature 455:1069-1075. PMID:18948947
  • Gonzalez-Garay M.L., Cranford SM, Braun MC, Doris PA. 2014. Diversity in the preimmune immunoglobulin repertoire of SHR lines susceptible and resistant to end-organ injury. Genes Immun. PMID: 25056448.
  • Brownstein CA, Beggs AH, Gonzalez-Garay M.L., et al. 2014. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge. Genome Biol.15(3):R53. PMID: 24667040.

  • Gonzalez-Garay M.L., McGuire AL, Pereira S, & Caskey CT (2013) Personalized genomic disease risk of volunteers. Proc Natl Acad Sci U S A. 110(42):16957-16962.

  • Gonzalez-Garay M.L.*#, Schaaf CP*#,  Xia, F*., Potocki, L., Gripp, K. W., Zhang, B., Peters, B. A., McElwain, M. A., Drmanac, R., Beaudet, A. L., Caskey, C. T., Yang, Y. (2013) Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism. Nat Genet. 45:1405-1408.

  • Gonzalez-Garay M.L.*, Burrows P.E.*, Rasmussen J. C.*, Aldrich M. B., Guilliod R., Maus E. A., Fife C. E., Kwon S., Lapinski P. E., King P. D. & Sevick-Muraca E. M. (2013) Lymphatic abnormalities are associated with RASA1 gene mutations in mouse and man. Proc Natl Acad Sci U S A 110(21):8621-8626. 

Mutations on MAGEL2 associated with Prader Willi