Patricia L. M. Dahia, MD, PhD

I am an MD, PhD with clinical training in Endocrinology and Metabolism and laboratory training in Cancer Genetics, Cellular and Molecular Biology. I am a tenured Professor of Medicine at the University of Texas Health Science Center at San Antonio (UTHSCSA) and the Mays Cancer Center at UTHSCSA and the holder of the Robert Tucker Hayes Distinguished Chair in Oncology. My career has focused on research in cancer genetics, with emphasis on pheochromocytomas and paragangliomas. Our work uncovering tumor susceptibility genes (including, SDHB, KIF1B, EPAS1/HIF2A, TMEM127, etc) has had both translational and biological impact. These studies helped define paradigms for pheochromocytoma and paraganglioma classification, genetic testing, patient surveillance, and innovative therapeutic modeling. Our translational and basic research uncovered links between energy metabolism, hypoxia, endosomal/lysosomal signaling and cancer susceptibility.

I have mentored over 50 trainees, many of whom have gone on to independent careers. I have been funded by Federal, State and Private grant agencies. I am currently funded by the NIH, Neuroendocrine Tumor Research Foundation (NETRF) and the VHL Alliance. Ongoing research in my team involves genotype-phenotype studies of pheochromocytoma, paraganglioma and other hereditary cancer predisposition, functional studies of susceptibility genes, and novel disease models, including organoids, to study these tumors.

I am the Director of the recently designated PheoPara Alliance Research and Clinical Center of Excellence at UTHSCSA.

• 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

  • Case report: Two sisters with a germline CHEK2 variant and distinct endocrine neoplasias.
  • Hypoxia Inducible factor 2 alpha (HIF2α) inhibitors: targeting genetically driven tumor hypoxia
  • Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor m
  • A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions
  • Thyroid nodules of indeterminate cytology in Hispanic/Latinx patients
  • Endocrine and Neuroendocrine Tumors Special Issue-Checkpoint Inhibitors for Adrenocortical Carcinoma and Metastatic Pheochromocy
  • Insights into Mechanisms of Pheochromocytomas and Paragangliomas Driven by Known or New Genetic Drivers
  • International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromoc
  • International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers
  • The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Management of Metastatic and/or Unrese
  • Genetic predisposition to neural crest-derived tumors: revisiting the role of KIF1B
  • Genotype-Phenotype Features of Germline Variants of the TMEM127 Pheochromocytoma Susceptibility Gene: A 10-Year Update
  • Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking
  • MYC Regulation of D2HGDH and L2HGDH Influences the Epigenome and Epitranscriptome
  • HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: Metastatic pheochromocytomas and paragangliom
  • Share Recognizing hypoxia in phaeochromocytomas and paragangliomas
  • Germline mutations in the new E1' cryptic exon of the VHL gene in patients with tumours of von Hippel-Lindau disease spectrum or
  • The tumor suppressor TMEM127 regulates insulin sensitivity in a tissue-specific manner
  • A synonymous VHL variant in exon 2 confers susceptibility to familial pheochromocytoma and von Hippel-Lindau disease
  • Molecular and phenotypic evaluation of a novel germline TMEM127 mutation with an uncommon clinical presentation
  • A Unique Case of Metastatic, Functional, Hereditary Paraganglioma Associated With an SDHC Germline Mutation
  • EPAS1 Mutations and Paragangliomas in Cyanotic Congenital Heart Disease
  • The TMEM127 human tumor suppressor is a component of the mTORC1 lysosomal nutrient-sensing complex
  • Molecular and phenotypic evaluation of a novel germline TMEM127 mutation with an uncommon clinical presentation
  • IDH Mutation, Competitive Inhibition of FTO, and RNA Methylation
  • Pheochromocytomas and Paragangliomas, Genetically Diverse and Minimalist, All at Once!
  • Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas
  • Recurrent Mutations of Chromatin-Remodeling Genes and Kinase Receptors in Pheochromocytomas and Paragangliomas
  • D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2
  • Next-generation sequencing for the diagnosis of hereditary pheochromocytoma and paraganglioma syndromes
  • Integrity of the pheochromocytoma susceptibility TMEM127 gene in patients with pediatric malignancies
  • Penetrance and clinical features of pheochromocytoma in a six-generation family carrying a germline TMEM127 mutation
  • Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity
  • The tumor susceptibility gene TMEM127 is mutated in renal cell carcinomas and modulates endolysosomal function
  • Next-generation sequencing for the genetic screening of phaeochromcytomas and paragangliomas: riding the new wave, but with caut
  • The genetic landscape of pheochromocytomas and paragangliomas: somatic mutations take center stage
  • A novel germline mutation in BAP1 predisposes to familial clear-cell renal cell carcinoma
  • Novel hereditary forms of pheochromocytomas and paragangliomas
  • In vivo and in vitro oncogenic effects of HIF2A mutations in pheochromocytomas and paragangliomas
  • MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma
  • An update on the genetics of paraganglioma, pheochromocytoma, and associated hereditary syndromes
  • Minireview: the busy road to pheochromocytomas and paragangliomas has a new member, TMEM127
  • MnSOD deficiency results in elevated oxidative stress and decreased mitochondrial function but does not lead to muscle atrophy d
  • Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations
  • Spectrum and prevalence of FP/TMEM127 gene mutations in pheochromocytomas and paragangliomas
  • VHL disease
  • Germline mutations in TMEM127 confer susceptibility to pheochromocytoma
  • Targeting of SMAD5 links microRNA-155 to the TGF-beta pathway and lymphomagenesis
  • Mutations of the metabolic genes IDH1, IDH2, and SDHAF2 are not major determinants of the pseudohypoxic phenotype of sporadic ph
  • High penetrance of pheochromocytoma associated with the novel C634Y/Y791F double germline mutation in the RET protooncogene
  • Integrity of the CBL gene in mature B-cell malignancies
  • Pheochromocytomas: from genetic diversity to new paradigms
  • A germline mutation of the KIF1B beta gene on 1p36 in a family with neural and nonneural tumors
  • The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor
  • Coordinated expression of microRNA-155 and predicted target genes in diffuse large B-cell lymphoma
  • Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma
  • Genetic analysis of high altitude paragangliomas
  • Transcription association of VHL and SDH mutations link hypoxia and oxidoreductase signals in pheochromocytomas
  • Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08
  • A RET mutation with decreased penetrance in the family of a patient with a "sporadic" pheochromocytoma
  • Evolving concepts in pheochromocytoma and paraganglioma
  • Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes
  • Novel pheochromocytoma susceptibility loci identified by integrative genomics
  • A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas
  • Distinct temporal genetic signatures of neurogenic and gliogenic cues in cortical stem cell cultures
  • Malignant pheochromocytoma: current status and initiatives for future progress
  • Hereditary endocrine neoplasias: fundamental insights and the practice of clinical cancer genetics
  • Identification and characterization of disease-related genes: focus on endocrine neoplasias
  • Genetic disorders of endocrine neoplasia. Introduction
  • Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial par
  • Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL1), in pheochromocytomas
  • Somatic mutation and germline variants of MINPP1, a phosphatase gene located in proximity to PTEN on 10q23.3, in follicular thyr
  • PTEN, a unique tumor suppressor gene
  • Somatic mitochondrial DNA (mtDNA) mutations in papillary thyroid carcinomas and differential mtDNA sequence variants in cases wi
  • PTEN suppresses breast cancer cell growth by phosphatase activity-dependent G1 arrest followed by cell death
  • Immunohistochemical evidence of loss of PTEN expression in primary ductal adenocarcinomas of the breast
  • Differences in allelic distribution of two polymorphisms in the VHL-associated gene CUL2 in pheochromocytoma patients without so
  • Mutation and deletion analysis of GFR alpha-1, encoding the co-receptor for the GDNF/RET complex, in human brain tumours
  • Pineal nitric oxide synthase, but not heme oxygenase, mRNA is suppressed by continuous exposure to light
  • The molecular pathogenesis of corticotroph tumors
  • Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET cod
  • PTEN is inversely correlated with the cell survival factor Akt/PKB and is inactivated via multiple mechanismsin haematological m
  • Germline PTEN mutations in Cowden syndrome-like families
  • Calcitonin deficiency in early stages of chronic autoimmune thyroiditis
  • Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors
  • Acute and subacute effects of endotoxin on hypothalamic gaseous neuromodulators
  • A highly conserved processed PTEN pseudogene is located on chromosome band 9p21
  • Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with g
  • Mutation and expression analysis of the p27/kip1 gene in corticotrophin-secreting tumours
  • Allelic imbalance, including deletion of PTEN/MMACI, at the Cowden disease locus on 10q22-23, in hamartomas from patients with C
  • Ectopic ACTH production by a bronchial carcinoid tumour responsive to desmopressin in vivo and in vitro
  • Induction of nitric oxide synthase and interleukin-1beta, but not heme oxygenase, messenger RNA in rat brain following periphera
  • Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome
  • Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918
  • Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors
  • Germline mutations in PTEN are present in Bannayan-Zonana syndrome
  • Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome
  • Expression of glucocorticoid receptor gene isoforms in corticotropin-secreting tumors
  • Mutation analysis of glial cell line-derived neurotrophic factor (GDNF), a ligand for the RET/GDNF receptor alpha complex, in sp
  • An inactivating mutation of the luteinizing hormone receptor causes amenorrhea in a 46,XX female
  • Deletion analysis of the p16 tumour suppressor gene in phaeochromocytomas
  • Vasopressin receptor expression and mutation analysis in corticotropin-secreting tumors
  • Mutations in the RET proto-oncogene and the von Hippel-Lindau disease tumour suppressor gene in sporadic and syndromic phaeochro
  • Molecular and immunohistochemical analysis of P53 in phaeochromocytoma
  • Further evidence for the lack of correlation between the breakpoint site within M-BCR and CML prognosis and for the occasional i
  • Low cord blood levels of catecholamine from a newborn of a pheochromocytoma patient