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Dr Dahia

Contact

210-567-4866

dahia@uthscsa.edu

Programs

  • M.D./Ph.D. in South Texas Medical Scientist Training Program
  • Ph.D. in Integrated Biomedical Sciences
  • Biology of Aging
  • Cancer Biology

Departments & Divisions

  • Department of Medicine
  • Division of Hematology & Oncology

Research

Research profile

Patricia L. M. Dahia, M.D., Ph.D.

Tenured Professor

School of Medicine

I am an M.D., Ph.D. with clinical training in Endocrinology and Metabolism and laboratory training in Cancer Genetics, Cellular and Molecular Biology. I am currently a tenured Professor of Medicine at the University of Texas Health Science Center at San Antonio (UTHSCSA). My career has been dedicated to research on the genetics of cancer, with emphasis on inherited endocrine tumors and discovery of cancer susceptibility genes (including PTEN, SDHB, KIF1B, EPAS1/HIF2A, TMEM127, etc). This work has had both translational and biological impact. On the translational level, our studies helped define paradigms for genetic testing, patient surveillance, and innovative therapeutic modeling, especially in the area of pheochromocytomas and paragangliomas. Our integrative genomics and signal transduction work uncovered links between energy metabolism, hypoxia, endosome/lysosomal signals and cancer susceptibility. In parallel to the ongoing gene discovery efforts through our patient sample repository (NCT03160274), current lines of investigation in my laboratory explore: a) the function of transmembrane protein TMEM127 tumor suppressor as a nutrient responsive lysosomal component and regulator of insulin sensitivity in vivo, b) epigenetic modulation by SDH and HIF mutations, and c) the epistatic interaction between in vivo hypoxia and HIF mutation (cyanotic congenital heart disease and paraganglioma, NEJM, 2018). We are also bringing our discoveries to the design and implementation of novel clinical trials in rare cancers (HIF2A inhibitor in metastatic paraganglioma, under FDA review). Throughout my independent career I have maintained continuous funding by Federal, State and Private grant agencies, have developed multidisciplinary collaborations and led multi-investigator consortia. I have mentored over 40 trainees at various levels, many of whom have gone on to independent careers in academia and industry. For the past two years I serve as the medical director of the UTHSCSA Clinical Translation Science Award (CTSA) activities to promote innovative clinical trial operations at UTHSCSA, and across CTSAs.

  • Professional Background

    Education

    • 1994 - PhD - Endocrine Genetics (Summa Cum Laude) - University of Sao Paulo, Sao Paulo, Brazil
    • 1988 - MD - Medicine - Federal University of Paraiba
    • Residency - Internal Medicine - Hospital das Clinicas, Univ. of Sao Paulo Sch. of Med.
    • Clinical Fellowship - Molecular Endocrinology - St. Bartholomew's Hospital, Univ. of London, UK
    • Clinical Fellowship - Endocrinology - Hospital das Clinicas, Univ. of Sao Paulo Sch. of Med.
    • Postdoctoral Fellowship - Cancer Genetics - Dana-Farber Cancer Institute, Harvard Medical School

    Appointments

    • 9/2015 - Tenured Professor - University of Texas Health Science Center at San Antonio (UTHSCSA), Medicine, San Antonio
    • 8/2005 - Faculty Member and Member of the Cancer Therapy and Research Center (CTRC) at UTHSCSA - University of Texas Health Science Center at San AntonioSan Antonio
  • Instruction & Training

    • 4/2019 - Present, Pre-Doctoral Student Supervision, UTHSCSA
    • 1/2019 - Present, Individual Instruction, University of Texas Health Science Center at San Antonio
    • 11/2016 - Present, Individual Instruction, UTHSCSA
    • 4/2016 - Present, Ph.D. Dissertations Directed, UTHSCSA
    • 2/2015 - Present, Post-Doctoral Student Supervision, UTHSCSA
  • Research & Grants

    Animal Models, Cancer Prevention, Genetics of Cancer, Genitourinary Cancer, Neuro-Oncology, Pediatric Cancer, mTOR Pathway

    Cancer Development and Progression Program 

    Research profile

    Grants

    Federal

    Funding Agency NIH-NCATS Title Institute for Integration of Medicine & Science (IIMS): A Partnership to Improve Health Status Active Period 5/2018 - 4/2023 Role Co-Investigator Grant Detail The vision of the Institute for Integration of Medicine and Science is to improve health and reduce disparities by
    accelerating scientific discoveries and applications across the full translational research spectrum. We will
    accomplish this by strategic resource deployment, focusing on prevalent challenges in our region, including: 1)
    the health needs of our underserved Hispanic and rural populations, 2) the special health issues facing activeduty
    military and veteran populations, and 3) limitations in the translational science workforce required to fill in
    critical knowledge gaps and improve health in South Texas and the US. I will serve in the capacity of Medical Director of the CTSA hub liaison team with the Trial Innovation Network Funding Agency NIH-NIGMS Title Interaction of the TMEM127 tumor suppressor with the mTORC1 lysosomal activating complex Status Active Period 6/2017 - 5/2022 Role Principal Investigator Grant Detail This proposal will examine the interaction between TMEM127 and the lysosomal protein complex involved in mTORC1 activation by nutrients. Funding Agency NIH-NIGMS Title Mechanisms of internalization and trafficking of the tumor suppressor and lysosomal membrane protein TMEM127 Status Active Period 1/2019 - 12/2020 Role Co-Investigator Grant Detail F31 Fellowship for Shahida K Flores, graduate student. Role: Mentor Funding Agency NIH-NIGMS Title Mechanisms of internalization and trafficking of TMEM127 (F31) Status Active Period 1/2019 - 12/2020 Role Co-Investigator Grant Detail   Funding Agency NIH-NRSA-NCI Title Cancer Biology- NCI-NRSA T32 training grant, predoctoral fellow Status Active Period 3/2017 - 12/2018 Role Contributor Grant Detail Shahida Flores, PhD candidate, was selected for the T32 Training Grant in Cancer Biology. This fellowship includes stipend, health insurance allowance and travel allowance for 12 months, renewable to 12 months.Award ended in Dec 2018, as the student was awarded an F31 NIH-NIGMS Fellowship Funding Agency NIA Title Biology of Aging- NIA T32 Training Grant, Postdoctoral Fellow Status Active Period 10/2015 - 9/2017 Role Contributor Grant Detail Subramanya Srikantan, PhD. Selected for Postdoctoral Fellowship within the T32 Training Grant in the Biology of Aging, NIA. One-year fellowship renewable for another year.

    Private

    Funding Agency Alex's Lemonade Stand Foundation for Childhood Cancer Title RNA methylation in metabolically disrupted pediatric cancers Status Active Period 10/2018 - 9/2020 Role Principal Investigator Grant Detail Innovator Award

    State

    Funding Agency Department of Medicine Pilot-UTHSCSA Title TMEM127 as an integrator of nutrient and growth factor signaling upstream of mTORC1 Status Active Period 1/2017 - 12/2017 Role Principal Investigator Grant Detail Pilot Grant- Dept. of Medicine Funding Agency Cancer Prevention and Research Institute of Texas (CPRIT) Title Investigation of the tumor suppressor TMEM127 on lysosome function and lipid metabolism Status Active Period 8/2014 - 7/2017 Role Principal Investigator Grant Detail This proposal will investigate the role of TMEM127 in the lysosome and its regulation of mTOR signaling.

     

    Funding Agency Nathan Shock Center of Excellence Pilot Program Title Tmem127, a novel tissue specific regulator of insulin sensitivity and lipogenesis Status Active Period 7/2019 - 6/2020 Role Principal Investigator Grant Detail The major goal of this project is to support in vivo clamp studies to evaluate the glucose/insulin metabolism of Tmem127 whole body and tissue-specific knockout models Funding Agency Mays Cancer Center Multi PI Pilot Title RNA Methylation in Metabolic Cancers -Translational Applications Status Active Period 3/2019 - 2/2020 Role Principal Investigator Grant Detail The major goal of this project is to support the generation of genetic models to study the contribution of RNA demethylases to cancers caused by oncometabolite imbalance, and optimize methylRNA sequencing approaches Funding Agency Mays Cancer Center Pilot Title Piloting the Development of a Program of Precision Medicine in Endocrine Cancers, from Biology to Prevention and Clinical Trials Status Active Period 1/2019 - 12/2019 Role Principal Investigator Grant Detail The major goal of this project is to establish a pipeline of genotyping rare endocrine cancers that can be used as the basis for health care decisions

  • Publications

      Journal Article

      Nada A. Farhat, James F. Powers,Annette Shepard-Barry, Patricia L. Dahia, Karel Pacak, Arthur S. Tischler. A previously unrecognized monocytic component of pheochromocytoma and paraganglioma Endocrine Pathology 2019 Jun;30(2):90-95. Flores SK, Cheng Z, Jasper AM, Natori K, Okamoto T, Tanabe A, Gotoh K, Shibata H, Sakurai A, Nakai T, Wang X, Zethoven M, Balachander S, Aita Y, Young W, Zheng S, Takekoshi K, Nakamura E, Tothill RW, Aguiar RCT, Dahia PLM. A synonymous VHL variant in exon 2 confers susceptibility to familial pheochromocytoma and von Hippel-Lindau disease J Clin Endocrinol Metab 2019 Apr;. Ong RKS,
      Flores SK,
      Reddick RL,
      Dahia PLM,
      Shawa H
      . A Unique Case of Metastatic, Functional, Hereditary Paraganglioma Associated With an SDHC Germline Mutation J Clin Endocrinol Metab 2018 Aug;103(8):2802-2806. Vaidya A,
      Flores SK,
      Cheng ZM,
      Nicolas M,
      Deng Y,
      Opotowsky AR,
      Lourenco DM Jr.,
      Barletta JA,
      Rana HQ,
      Pereira MA,
      Toledo RA,
      Dahia PLM. EPAS1 Mutations and Paragangliomas in Cyanotic Congenital Heart Disease N Engl J Med 2018 Mar;378(13):1259-1261. Deng Y,
      Qin Y,
      Srikantan S,
      Luo A,
      Cheng ZM,
      Flores SK,
      Vogel KS,
      Wang E,
      Dahia PLM. The TMEM127 human tumor suppressor is a component of the mTORC1 lysosomal nutrient sensing complex Hum Mol Genet 2018 Mar;27(10):1794-1808. The, N.G.S.i.P.S.G., Toledo, R.A., Burnichon, N., Cascon, A., Benn, D.E., Bayley, J.-P., Welander, J., Tops, C.M., Firth, H., Dwight, T., Ercolino, T., Mannelli, M., Opocher, G., Clifton-Bligh, R., Gimm, O., Maher, E.R., Robledo, M., Gimenez-Roqueplo, A.-P. & Dahia, P.L.M. Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas Nature Reviews Endocrinology 2017 Jan;13:233-247. Elkashef SM, Lin AP, Myers J, Sill H, Jiang D, Dahia PLM, Aguiar RCT. IDH Mutation, Competitive Inhibition of FTO, and RNA Methylation Cancer Cell 2017 Jan;31:619-620. Deng Y, Flores SK, Cheng Z, Qin Y, Schwartz RC, Malchoff C, Dahia PLM. Molecular and phenotypic evaluation of a novel germline TMEM127 mutation with an uncommon clinical presentation Endocrine-Related Cancer 2017 Jan;24:L79-L82. Dahia PL. Pheochromocytomas and Paragangliomas, Genetically Diverse and Minimalist, All at Once! Cancer Cell 2017 Jan;31:159-161. Rodrigo A. Toledo,Yuejuan Qin, Zi-Ming Cheng, Qing Gao, Shintaro Iwata,
      Gustavo M. Silva, Manju L. Prasad, I. Tolgay Ocal, Sarika Rao, Neil Aronin,
      Marta Barontini, Jan Bruder, Robert L. Reddick, Yidong Chen, Ricardo C.T. Aguiar,
      Patricia L Dahia. Recurrent Mutations of Chromatin-Remodeling Genes and Kinase Receptors in Pheochromocytomas and Paragangliomas Clin Cancer Res 2015 Dec;:1-10. Lin AP, Abbas S, Kim SW, Ortega M, Bouamar H, Escobedo Y, Varadarajan P, Qin Y, Sudderth J, Schulz E, Deutsch A, Mohan S, Ulz P, Neumeister P, Rakheja D, Gao X, Hinck A, Weintraub ST, DeBerardinis RJ, Sill H, Dahia PL, Aguiar RC. D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2 Nat Commun 2015 Jul;6:7768-7768. King EE, Qin Y, Toledo RA, Luo A, Ball E, Faucz FR, Janeway KA, Stratakis CA, Tomlinson G, Dahia P, Dahia PL. Integrity of the pheochromocytoma susceptibility TMEM127 gene in pediatric malignancies Endocr Relat Cancer 2015 Mar;22(3):L5-L7. Qin Y, Deng Y, Ricketts CJ, Srikantan S, Wang E, Maher ER, Dahia PL. The tumor susceptibility gene TMEM127 is mutated in renal cell carcinomas and modulates endolysosomal function Hum Mol Genet 2014 May;23(9):2428-2439. Kugelberg J, Welander J, Schiavi F, Fassina A, Backdahl M, Larsson C, Opocher
      G, Soderkvist P, Dahia PL, Neumann HP, Gimm O. Role of SDHAF2 and SDHD in von Hippel-Lindau Associated Pheochromocytomas World Journal of Surgery 2014 Mar;38:724-732.

      Not Specified

      Srikantan S, Deng Y, Cheng ZM, Luo A, Qin Y, Gao Q, Sande-Docor GM, Tao S, Zhang X, Harper N, Shannon CE, Fourcaudot M, Li Z, Kasinath BS, Harrison S, Ahuja S, Reddick RL, Dong LQ, Abdul-Ghani M, Norton L, Aguiar RCT, Dahia PLM. The tumor suppressor TMEM127 regulates insulin sensitivity in a tissue-specific manner Nature Communications 2019 Oct;10(4720):1-17.

      Review Article

      Toledo RA, Dahia PL. Next-generation sequencing for the diagnosis of hereditary pheochromocytoma and paraganglioma syndromes Curr Opin Endocrinol Diabetes Obes 2015 Jun;22(3):169-179.

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