Lehman, Donna MSchool of Medicine |
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Associate Professor in the Division of Clinical Epidemiology, Department of Medicine with a secondary appointment in the Department of Epidemiology and Biostatistics. My primary research interest is in the identification of genetic factors that influence human complex traits and disorders. The current focus of my lab is to identify genes that are involved in the pathogenesis of type 2 diabetes and related metabolic traits among the Mexican American population using large cohort studies. We are using whole genome high-throughput methodology to screen the human genome and have identified multiple loci harboring genetic variants affecting risk for diabetes. Our goal now is to explore their functional effects in the etiology of disease. We have developed a new methodology in my lab for this purpose which is the application of induced pluripotent stem (iPS) cell technology to complex disease genetics. This technology will help us to explore biological effects of genetic variation on a whole-genome scale in multiple disease-relevant cell types. In addition to standard DNA sequence variation, we are examining the extent and effect of genome-wide structural variation on gene expression and disease. Copy number variation (CNV) is a type of structural variation that is abundant in the human genome. We are utilizing very large extended pedigree cohorts and samples to investigate both common and rare CNVs and assess environmental and aging influences on the structural variation itself. We are also investigating the role of CNVs in risk for prostate cancer. |
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| 9/2008 - Present | Associate Professor | UT Health Science Center San Antonio, Medicine, San Antonio, TX |
| Year | Degree | Discipline | Institution |
| 1999 | PhD | Cellular and Structural Biology | University of Texas Health Science Center San Antonio , TX |
| 1994 | MS | Biomedical Science | University of Tennessee Knoxville , TN |
| 1985 | BS | Biology (Summa Cum Laude) | Texas A&M University College Station , TX |
1. iPS cell technology- A new focus of my lab is the generation and use of human induced pluripotent stem (iPS) cells for complex disease genetics. For many complex disorders, the disease relevant tissue is not accessible for functional analyses of genetic changes. The generation of pluripotent cells from accessible adult somatic cells, which contain the entire genome of that individual, can aid in assessing functional consequences of a genetic alteration in appropriate context. Differentiation of iPSC colonies into select cell types can generate disease-relevant cellular models with which to test physiologic consequences of the total genetic variation of an individual. My lab has produced human iPSCs which we have differentiated into neurites, adipocytes and cardiomyocytes. This preliminary data has led to the Feb 2012 submission of an R01 application to the NIDDK entitled "Personal human cellular models for resolving genetic variation in complex traits." |
2. Human Genetics and Genetic Epidemiology- My primary research interests have been in the identification of genetic factors that influence human traits and disorders whose etiology is very complex involving the interactions between multiple genetic pathways and the environment. My lab is using whole-genome high-throughput methodologies to identify genetic changes that are involved in the pathogenesis of type 2 diabetes and related metabolic traits, and prostate cancer among the Mexican American population using large cohort studies. We have identified several genomic loci. Our goal now is to isolate the causal DNA changes influencing disease and explore their functional effects in the etiology of disease. We are applying iPS cell technology for this purpose. We are also assessing the effect of genome-wide structural variation on gene expression and disease. Copy number variation (CNV) is a type of structural variation that is abundant in the human genome. We are utilizing very large extended pedigrees to investigate both common and rare CNVs and assess environmental and aging influences on the structural variation itself. |
3. Public Health Genomics and Medical Genomics- I direct a genetics elective in the Master of Science in Clinical Investigation Program (MEDI6067) that is oriented toward all health professions with the aim of familiarizing students with current concepts and methods used in patient-oriented genetic studies. A main objective is for the students to understand the potential and current limits of personalized medicine as well as the ethical issues involved. I also co-direct CSBL6165 "Medical Genetics" course that covers important clinical aspects of genetics including genetic counseling,reproductive genetics, dysmorphology, inherited cancers, prenatal diagnosis and newborn screening. Diagnosis and current research toward treatment and cure of common genetic disorders are discussed. This course helps prepare fellows for the American Board of Obstetrics and Gynecology, Maternal Fetal Medicine subspecialty board exams. |
| Date | Description | Institution | # Students |
| 11/2011 - Present | Pre-Doctoral Student Supervision | UT Health Science Center San Antonio | |
| 9/2011 - 9/2014 | FAME program instruction | UTSA and UTHSCSA | 30 students |
| The Facilitated Acceptance to Medical Education [FAME] Program is an innovative and fully integrated pilot program being designed to lead to the award of both baccalaureate and Doctor of Medicine degrees in a 7yr timeframe. I am involved with developing and teaching the genetics undergraduate course to be co-taught by Dr. Aaron Cassill (UTSA) and myself beginning Fall 2012. | |||
| 6/2010 - Present | Integrate Mol/Bio/Patient Res | The University of Texas Health Science Center | 15 students |
| This course is "Integrating Molecular Biology into Paitent Research". I provide a lecture and lead discussion covering the current status of and techniques used in genetics research of complex diseases. | |||
| 5/2010 - Present | Post-Doctoral Student Supervision | UT Health Science Center San Antonio | |
| 6/2009 - Present | Pre-Doctoral Student Supervision | UT Health Science Center San Antonio | |
| 9/2008 - Present | CSBL 6165 Medical Genetics | 3 students | |
| Co-Course Director - This 3-semester credit hour elective was developed by myself and Dr. Charleen Moore. It is designed as an advanced genetics course for graduate students as well as a course to fulfill medical genetics training requirements and preparation for Boards for MD Fellows in Reproductive Endocrinology, Maternal Fetal Medicine, and Pediatrics. The course begins with an advanced review of basic genetic concepts and then covers medical genetic content including genetic counseling and pedigree analysis, prenatal diagnosis and reproductive genetics, newborn screening, developmental genetics and dysmorphology, and inherited cancers. Diagnosis and current research toward treatment and cure of common genetic disorders and related ethical issues are also a focus. | |||
| 1/2008 - Present | CSBL 5073 Genetics, Genomics and Development Core Course | 11 students | |
| CSBL 5073, Genetics, Genomics and Development is the required core course for all PhD graduate students entering the Integrated Multidisciplinary Graduate Program (IMGP) in the Genetics, Genomics & Development (GGD) track and is an elective for other IMGP students. It is taught each spring semester. I provide "QTLs/Complex Disorders" 1.5 hr lecture and paper discussion, and participate in the exam development and grading. | |||
| 1/2007 - Present | Genetics and Genetic Epidemiology | The University of Texas Health Science Center | 7 students |
| Course Director - This 1-hour credit course was developed by me as part of the Masters of Science in Clinical Investigation (MSCI) program. It covers current concepts and methods used in patient-oriented genetic studies to provide the students the necessary foundation to both interpret results from a wide range of human genetic studies and design studies to answer their own translationally relevant research questions. The course utilizes lectures, which are given by me and a number of local experts that I coordinate with, as well as assignments and student presentations. I direct the course each Spring semester. Students have come from the MSCI program as well as non-degree seeking K-scholars. | |||
| 6/2006 - Present | UTHSCSA | ||
Journal Article |
| Lehman DM, Lorenzo C, Hernandez J, Wang CP. Statin use as a moderator of metformin effect on risk for prostate cancer among type 2 diabetic patients Diabetes Care 2012 May;35(5):1002-1007. |
| Farook VS, Puppala S, Schneider J, Fowler SP, Chittoor G, Dyer TD, Allayee H, Cole SA, Arya R, Black MH, Curran JE, Almasy L, Buchanana TA, Jenkinson CP, Lehman DM, Watanabe RM, Blangero J, Duggirala R. Metabolic Syndrome is linked to Chromosome 7q21 and associated with genetic variants in CD36 and GNAT3 in Mexican Americans Obesity 2012 Mar;. |
| Yao JW et al. and Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy Diabetes Care 2012 Jan;35(3):556-564. |
| Blackburn A, Dean A,Lehman DM. Imputation in families using a heuristic phasing approach BMC Proceedings 2012 Jan;. |
| Farook Thameem, Sobha Puppala, Donna M Lehman, Michael P. Stern, John Blangero, Hanna E. Abboud, Ravindranath Duggirala, Samy L Habib. The Ser(326)Cys polymorphism of 8-OxoGuanine Glycosylase 1 (OGG1) is associated with Type 2 Diabetes in Mexican Americans Human Heredity 2010 Jun;70:97-101. |
| Coletta DK, Schneider J, Hu SL, Dyer TD, Puppala S, Farook VS, Arya R, Lehman DM, Blangero J, DeFronzo RA, Duggirala R, Jenkinson CP. Genome-wide linkage scan for genes influencing plasma triglyceride levels in the Veterans Administration Genetic Epidemiology Study Diabetes 2009 Jan;58(1):279-284. |
| Puppala S, Arya R, Thameem F, Arar NH, Bhandari K, Lehman DM, Schneider J, Fowler S, Farook VS, Diego VP, Almasy L, Blangero J, Stern MP, Duggirala R, Abboud HE. Genotype by diabetes interaction effects on the detection of linkage of glomerular filtration rate to a region on chromosome 2q in Mexican Americans Diabetes 2007 Nov;56(11):2818-2828. |
| Goodarzi MO, Lehman DM, Taylor KD, Guo X, Cui J, Quiones MJ, Clee SM, Yandell BS, Blangero J, Hsueh WA, Attie AD, Stern MP, Rotter JI. SORCS1: a novel human type 2 diabetes susceptibility gene suggested by the mouse Diabetes 2007 Jul;56(7):1922-1929. |
Abstract |
| Wood AR, Jun G, Cingolani P, Almeida M, Fuchsberger C, Dyer TD, Curran JE, Grundstad J, Blackwell TW, Teslovich TM, Lehman DM, Grossman R, Laramie JM, Lincoln SE, Boehnke M, McCarthy MI, Frayling TM, Sladek R, Duggirala R, Blangero J, Abecasis GR, T2D-GENES Consortium. Understanding the contribution of genomic variants from across the full allele frequency spectrum to diabetes related traits; 2012 Jun. (Diabetes; vol. 61, no. S1). |
| Almeida M, Jun G, Teslovich TM, Wood AR, Frayling TM, Fuchsberger C, Cingolani P, Blackwell TW, Dyer TD, Curran JE, Lehman DM, Sladek R, Grunstad J, Grossman R, Laramie JM, Lincoln SE, McCarthy MI, Boehnke M, Duggirala R, Abecasis GR, Blangero J, T2D-GENES Consortium. Whole genome sequencing to discover type 2 diabetes risk genes in Mexican American pedigrees: T2D-GENES consortium project 2; 2012 Jun. (Diabetes; vol. 61, no. S1). |
| Ghittoor G, Puppala S, Fowler SP, Farook VS, Schneider J, Resendez RG, Hunt KJ, Bradshaw BS, Cersosimo E, Arya R, Almasy L, Curran JE, Comuzzie AG, Lehman DM, Jenkinson CP, Lynch JL, DeFronzo RA, Blangero J, Hale DE, Duggirala R. Genetic architecture of bone mass related traits and their correlatio with metbolic syndrome components in Mexican American children; 2012 Jun. (Diabetes; vol. 61, no. S1). |
| Jun G, Almeida M, Cingolani P, Wood, AR, Fuchsberger C, Teslovich TM, Dyer TD, Curran JE, Grunstad J, Blackwell TW, Lehman DM, Grossman R, Lincoln SE, Laramie JM, Boehnke M, McCarthy MI, Frayling TM, Sladek R, Duggirala R, Blangero J, Abecasis GR. Detecting functional rare variants relating to type 2 diabetes using deep whole genome sequencing; 2012 Jun. (Diabetes; vol. 61, no. S1). |
| Fowler SP, Puppala S, Farook VS, Schneider J, Chittoor G, Resendez RG, Hunt KJ, Bradshaw BS, Cersosimo E, Arya R, Almasy L, Curran JE, Comuzzie AG, Lehman DM, Jenkinson CP, Lynch JL, DeFronzo RA, Blangero J, Hale DE, Duggirala R. Genetics of metabolic syndrome in Mexican American children: The San Antonio Family Assessment of Metabolic Risk Indicators in Youth (SAFARI) Study; 2012 Jun. (Diabetes; vol. 61, no. S1). |
| Wang C-P and Lehman DM. Combination treatment with metformin and statins shows enhanced effect on reducing risk of prostate cancer; 2011 Jan. (Diabetes; vol. 60, no. S1). |
| Lehman DM, Dean A, Curran JE, Carless M, Puppala S, Fowler S, Leach RJ, Arya R, Duggirala R, Blangero J, Goring HHH. Enrichment of Diabetes and CVD eQTLs in Mexican Americans; 2011 Jan. (Diabetes; vol. 60, no. S1). |
| Lehman DM. Germline and somatic CNVs in 4 Mexican American monozygotic twin pairs; 2010 Nov. (American Society of Human Genetics). |
| Farook V, Schneider J, Fowler S, Puppala S, Curran JE, Arya R, Almasy L, Comuzzie AG, Jenkinson CP, Lehman DM, DeFronzo R, Blangero J, Hale DE, Duggirala R, Lynch JL. Increased Prevalence of Elevated Liver Enzyme in Obesity and Related Conditions and Its Genetic Determinants in Mexican American Children; 2009 Jan. (Diabetes; vol. 58, no. S1). |
| Blackburn A., Gelfond J., Goring H.H., Beuten Y., Thompson I., Leach RJ, and Lehman DM. Identification of Copy Number Variable Regions (CNVRs) Associated with Risk of Prostate Cancer in Mexican-Americans Abstract presented at 59th Annual meeting of the American Society of Human Genetics, Honolulu HI, October 2009; 2009 Jan. (American Society of Human Genetics). |
| Fowler S, Diego VP, Puppala S, Schneider J, Farook V, Lynch JL, Hunt KJ, Curran JE, Arya R, Lehman DM, Almasy L, Comuzzie AG, Jenkinson CP, Stern MP, DeFronzo R, Glangero J, Duggirala R, Hale DE. Interaction between Genotype and Sedentary Lifestyle Influences Obesity and Insulin Resistance Measures in Mexican American Children; 2009 Jan. (Diabetes; vol. 58, no. S1). |
| Sosa E, Resendez RG, Puppala S, Schneider J, Fowler S, Farook V, Lynch JL, Arya R, Almasy L, Comuzzie A, Jenkinson CP, Lehman DM, DeFronzo R, Blangero J, Duggirala R, Hale DE. Risk of eating disorders: genetic architecture and correlation with measures of obesity in Mexican American children; 2009 Jan. (Diabetes; vol. 58, no. S1). |
| Puppala S, Schneider J, Fowler S, Farook V, Cersosimo E, Lynch JL, Arya R, Almasy L, Comuzzie AG, Jenkinson CP, Lehman DM, DeFronzo R, Blangero J, Duggirala R, Hale DE. Increased Occurrence of Childhood Obesity and Its Correlates and Their Genetic Architecture in Mexican American Children; 2009 Jan. (Diabetes; vol. 58, no. S1). |
| Lehman DM, Beuten J, Puppala S, Leach RJ, Arya R, Duggirala R, Blangero J, Goring HH, Stern MP. VTI1A on chromosome 10q is associated with diabetes in Mexican Americans; 2008 Jan. (Diabetes; vol. 57, no. S1). |
| Arya R, Thameem F, Jenkinson CP, Puppala S, Farook VS, Abboud HE, Stern MP, Blangero J, Lehman DM, Duggirala R. Associations of variants in peroxisome proliferator activated receptor gamma coactivator1 (PPARGC1) gene with obesity and type 2 diabetes in Mexican Americans; 2008 Jan. (Diabetes; vol. 57, no. 1). |
| Arya R, Thameem F, Jenkinson CP, Puppala S, Farook VS, Abboud HE, Stern MP, Blangero J, Lehman DM, Duggirala R. Association of variants in peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene with obesity and type 2 diabetes (T2D) in Mexican Americans; 2008 Jan. (Diabetes; vol. 57, no. S1). |
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| Funding Agency | NIH |
| Title | Discovery of Functional Variants in Type 2 Diabetes Genes in Mexican Americans (1U01DK085524-01) |
| Status | Active |
| Period | 9/2009 - 9/2014 |
| Role | Co-Principal Investigator |
| Grant Detail | This U01 cooperative agreement will conduct genetic studies in 5 Mexican American cohorts from San Antonio. Investigators selected through this FOA now comprise a Steering Committee to develop the Multi-Ethnic Study of Diabetes Genes with the aim of confirming and characterizing the genetic associations for type 2 diabetes identified from Genome Wide Association Studies (GWAS) studies in multiple ethnic groups that make up the worldwide population. |
| Funding Agency | NIH |
| Title | Metformin, Statins, and Prostate Cancer Prevention in Type 2 Diabetes |
| Status | Active |
| Period | 9/2012 - 8/2014 |
| Role | Principal Investigator |
| Grant Detail | This project is using longitudinal data from the National VA databases to examine the effects of combination therapy by metformin and statins on prostate cancer (PCa) incidence and progression. Specific Aims 1) to identify measurements necessary to assess the independent effects of metformin and statins on PCa incidence that are mediated by the glucose-lowering and lipid-lowering effects; 2) to assess the independent effects of metformin and statins on PCa incidence mediated/moderated by the glucose-lowering and lipid-lowering effects; 3) to assess the joint effect of metformin and statins on PCa incidence reduction. |
| Funding Agency | NIH/NIDDK |
| Title | NIDDM Susceptibility Genes in Mexican Americans |
| Status | Active |
| Period | 9/2006 - 8/2013 |
| Role | Principal Investigator |
| Grant Detail | In NCE. Genetic risk factors for type 2 diabetes in the Mexican American population has been localized to a region on chromosome 10 in the San Antonio Family Diabetes Study. The goal of this project is to identify the genetic variants in this region that are linked to disease. We are using high-throughput molecular genetic methodologies and re-sequencing in this cohort. |
| Funding Agency | Department of Defense |
| Title | Assessing the role of copy number variants in prostate cancer risk and progression using a novel genome-wide screening method |
| Status | Active |
| Period | 9/2009 - 8/2013 |
| Role | Principal Investigator |
| Grant Detail | |
| Funding Agency | NIH |
| Title | Type 2 Diabetes Gene Discovery Linked to 3p in Hispanics |
| Status | Active |
| Period | 8/2007 - 6/2012 |
| Role | Principal Investigator |
| Grant Detail | A study which aims to identify the genes in a chromosomal region of 3p that influence diabetes susceptibility and related traits in Mexican Americans. |