Dr. Andres Hernandez-Garcia, MD,PhD - BAYLOR COLLEGE OF MEDICINE - SCIENTIST STAFF & LAB. MANAGER & RESEARCH CLINICAL COORDINATOR

Dr. Andres Hernandez-Garcia

MD,PhD

BAYLOR COLLEGE OF MEDICINE

SCIENTIST STAFF & LAB. MANAGER & RESEARCH CLINICAL COORDINATOR

HOUSTON , TEXAS | United States

Main Specialties: Biochemical Genetics, Medical Genetics, Molecular Genetic Pathology

Additional Specialties: MEDICAL GENETICS AND MOLECULAR BIOLOGY

ORCID logohttps://orcid.org/0000-0002-5343-5513


Top Author

Dr. Andres Hernandez-Garcia, MD,PhD - BAYLOR COLLEGE OF MEDICINE - SCIENTIST STAFF & LAB. MANAGER & RESEARCH CLINICAL COORDINATOR

Dr. Andres Hernandez-Garcia

MD,PhD

Introduction

Dr Hernández-García is an exceptionally well qualified geneticist, who received his PhD, from Universidad Autónoma de Nuevo Leon. In 2003, Dr. Hernández-Garcia was the founder of the Biomedical Research Center at Universidad Autónoma de Coahuila, México. Along with his position as a full time Professor Category “C” at Faculty of Medicine, Universidad Autónoma de Coahuila, he became the Dean of the College of Medicine, Biomedical Research Center, General University Hospital and Pediatrics University Hospital of the Universidad Autónoma de Coahuila during the period of March, 1992 to March, 1996. He was also the Founder, Chairman and Consultant of Genetics Department at Faculty of Medicine and University Hospitals of Torreón, Coah. México.
He was a Council Member of the Mexican Association of Faculties and Schools of Medicine and Council Member of the National Certification Program of Faculties and Schools of Medicine of México. Furthermore, he was a contributor in the elaboration of The General Design of Mexican Medical Education Quality Program and active participant in the “Creation of Quality Standards in Mexican Medical Education used in The National Certification System for Mexican Medical Schools”.
With such an extraordinary training and education background Dr. Hernandez- Garcia returned to work in his hometown and former medical school to improve and elevate the standards of medical education and to contribute immensely to medical research of the local community in the city of Torreón, state of Coahuila, Mexico. Some of his recognitions include:
1. - Best Abstract Award at the 4th Annual CVRI Symposium. Baylor College of Medicine Cardiovascular Research Institute. February 4, 2016, 2. - Peer reviewer for Science magazine PLOS ONE (Since 2012), 3. - Molecular Surgeon Young Investigator Award. Michael E. DeBakey Department of Surgery. Baylor College of Medicine. December 19, 2008. Houston, TX. USA. 4. - Award National System for Researchers. Consejo Nacional de Ciencia y Tecnología, México. 2006/2008. 5. - Award in Health Sciences Research UANL-2002. Granted by Universidad Autónoma de Nuevo León. México. September 2003, 6. - Awards in Basic Sciences Research and Clinical Research (1987, 1988.). Universidad Autónoma de Nuevo León México. 7. - Miguel Ramos Arizpe Medal for Academic Worth. Universidad Autónoma de Coahuila. México. 8. - He was once declared Distinguish Citizen by his hometown. (1994).
Dr. Hernández-García earned his medical degree with honors from Universidad Autónoma de Coahuila, México. He served a rotating internship Residency in Biomedical Research at Unidad de Investigación Biomédica IMSS, Centro Médico Nacional. México, D.F. He earned the Specialty in Medical Genetics degree from Instituto Nacional de la Nutrición Salvador Zubirán and Universidad Nacional Autónoma de México. He also spent one year in Master in Education. Universidad Iberoamericana. Campus Laguna, México. Additionally, he earned his Ph.D. in Molecular Biology and Genetic Engineering from the Universidad Autónoma de Nuevo León México. The Promotions Committee recommended award his Ph.D. With the “Magno Cum Lauro” honor.
Dr. Hernandez-Garcia admirable spirit and tenacity to reach excellence is further underscored by the fact that despite his most abundantly clear educational and research accomplishments in Mexico he did not consider his career yet completed. Instead, he came to the United States and further his research by completing an a Postdoctoral Research Fellow in the Department of Pediatric-Hematology/ Oncology, Texas Children’s Hospital in November, 1998, then he continued with his research education further as a Post-doctoral research fellow in the Department of Radiology/Radiation Oncology, Veterans Affairs Medical Center until 31 May, 2001. Lastly, he served for 9 years as a Faculty member at the General Surgery Division of the Michael E. DeBakey Department of Surgery at Baylor College of Medicine (June 01, 2001- May 31, 2009).
During this time he had obtained invaluable experience in the field of gene therapy clinical trials, handling of naive immunodeficient mice, micro surgery, immunohistochemistry/histology, cell culture, animal models, and Molecular Biology Techniques.
Dr. Hernandez-Garcia has been working enthusiastically to delineate the Integration of Cell Signaling Pathways during Liver Regeneration and carcinogenesis. Additionally, his scientific work has made an outstanding contribution in the study of the immunological response against adenoviral vectors, his results in this specific field has been published in a specialized journal with high factor impact in the scientific field (Impact of preimmunization on adenoviral vector expression and toxicity in a subcutaneous mouse cancer model. Molecular Therapy. 2002 Sep; 6 (3): 342-8.)
Dr. Hernandez always had a considerable inclination for biomedical research and teaching and because of this he was always looking for opportunities to gain further knowledge and skills in those areas. His interest in translational research rapidly move up toward the field of suicide gene therapy as a form of drug delivery system that allows for negative selection of malignant cells using a prodrug approach. In this approach malignant cells are transfected with suicide genes, which are genes that mediate the conversion of an inactive drug (“prodrug”) into an agent that is toxic to the cell. The goal will be ensure the presence and expression of suicide genes in as many cancer cells as possible while limiting their presence or expression in normal cells.
After this awesome experience Dr. Hernández-García was able to acquire superior clinical skills and research tools to promptly assume a prominent role in the field of Human genetics.
In keeping with his already ascending career and focused direction to accomplish his professional goals in the medical sciences, Dr. Hernandez has engaged in the pursuit of important basic and translational research within the context of the Molecular and Human Genetics Department at Baylor College of Medicine (since 2009 to date). Currently, he has been actively dedicated to identifying and characterizing genes that cause common, life-threatening birth defects and determining the molecular mechanisms by which they impact human health.
He have been particularly successful in using a combination of cytogenetic data and mouse modeling to understand the molecular and biological pathways involved in the development of congenital diaphragmatic hernia (CDH). Since up to 40% of individuals with CDH also have cardiac defects, many of the genes under his research study—including NR2F2, GATA4, ZFPM2, TBX2 and SOX7—play a critical role in both CDH and cardiovascular development. As a result, his research efforts are becoming increasingly cardiac-focused.
Currently, he is working with Sox7 and Rere conditional knockout mice which will aid us in identifying the molecular mechanisms by which SOX7 and/or RERE deficiency causes abnormalities in embryonic cardiac development and postnatal cardiac function. Recurrent microdeletions of chromosome 8p23.1 that include SOX7 area are associated with a high risk of developing cardiovascular malformations. The results of Dr. Hernandez-Garcia research suggest that deletion of SOX7 may contribute to the development of cardiovascular malformations associated with recurrent 8p23.1 microdeletions.
Most importantly, Dr. Hernandez Garcia has strengthened his research initiative by developing strong collaborative relationships at Baylor College of Medicine and Texas Medical Center with established leaders in the field of Cardiovascular Development, and Human Genetics who have agreed to collaborate with him during the development of his research career development program.
Dr. Hernandez-Garcia has made valuable research contributions in the area of human genetics and gene therapy, he has vast experience in biomedical research and his scientific work has been published in multiple papers, book chapters and abstracts as detailed in his curriculum vitae.
Since his arrival to Baylor College of medicine and the Michael E. DeBakey Veterans Affairs medical Center, Dr. Hernandez has demonstrated that he has an avid interest for translational basic science research. Therefore, The Molecular and Human Genetics Department of Baylor College of Medicine have made a strong commitment to provide Dr. Hernandez with every resource necessary to give him an optimal environment to conduct advanced basic science and translational research taking results from in-vivo animal work to patients at the bedside and confer his research activities a high clinical relevance, since advances in this area of research could potentially have an enormous impact on the health and well-being of human beings as well as on the cost of health care delivery in the United States.

Primary Affiliation: BAYLOR COLLEGE OF MEDICINE - HOUSTON , TEXAS , United States

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Research Interests:


View Dr. Andres Hernandez-Garcia’s Resume / CV

Education

Jan 2017
Baylor College of Medicine Department of Molecular and Human Genetics
Scientist, Staff
Department of Molecular and Human Genetics
Jan 2017
Baylor College of Medicine Department of Molecular and Human Genetics
Scientist, Staff
Department of Molecular and Human Genetics
Jan 2009 - Jan 2016
Baylor College of Medicine Department of Molecular and Human Genetics
Postdoctoral Associate
Department of Molecular and Human Genetics
Jun 2001
Veterans Affairs Medical Center and Baylor College of Medicine. June, 2001 to June, 2009.
Research Instructor
Michael E. DeBakey Department of Surgery
Jan 2000 - Jan 2001
Baylor College of Medicine Michael E DeBakey Department of Surgery
Postdoctoral Research Associate
Department of Radiology/Radiation Oncology,
Jan 1998 - Jan 2001
Universidad Autónoma de Nuevo León Facultad de Medicina
Ph D. in Molecular Biology and Genetic Engineering
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1998 - Jan 2000
Texas Children's Hospital/Baylor College of Medicine
Postdoctoral Fellow
Department of Pediatric-Hematology/ Oncology. Texas Children’s Hospital. Houston Tx.
Jan 1978 - Jan 1980
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran
Specialty in Medical Genetics
GENETICS
Jan 1970 - Jan 1975
Universidad Autónoma de Coahuila Facultad de Medicina Unidad Torreón
Medical Doctor

Experience

Oct 2018
Down-regulation of Sox7 impairs epithelial-to-mesenchymal transition and endocardial cushion morphogenesis.
Platform Conference Featured Speaker
PLATFORM (oral) presentation at the 2018 American Society of Human Genetics Annual Meeting in San Diego, California from October 16-20, 2018.
Oct 2016
SOX7 deficiency impairs embryonic vasculogenesis and epithelial-to-mesenchymal transition during atrioventricular endocardial cushion development
ASHG 2016 Annual Conference Poster Special Recognition Award
Reviewers' Choice Abstract, by the American Society of Human Genetics Conference Committee 2016 at Vancouver, Canada..
Feb 2016
Best Abstract Award at the 4th Annual Cardiovascular Research Institute Symposium. Baylor College of Medicine.
Conference Featured Speaker
Best Abstract Award at the 4th Annual Cardiovascular Research Institute Symposium. Baylor College of Medicine. February 4, 2016. Houston, TX. USA.
Jun 2001 - May 2009
Baylor College of Medicine
RESEARCH INSTRUCTOR
SURGERY
Mar 1992 - Mar 1996
Universidad Autonoma de Coahuila - Unidad Torreón
Dean of College of Medicine
DIRECCION GENERAL
Mar 1992 - Mar 1996
Universidad Autónoma de Coahuila Facultad de Medicina Unidad Torreón
Dean of Pediatrics University Hospital
Hospital Infantil Universitario en Torreón

Publications

27Publications

734Reads

16Profile Views

119PubMed Central Citations

RERE deficiency leads to decreased expression of GATA4 and the development of ventricular septal defects.

Dis Model Mech 2018 08 28;11(9). Epub 2018 Aug 28.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA

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http://dx.doi.org/10.1242/dmm.031534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176990PMC
August 2018
15 Reads
4.973 Impact Factor

De Novo Mutations of RERE Cause a Genetic Syndrome with Features that Overlap Those Associated with Proximal 1p36 Deletions

The American Journal of Human Genetics Available online 14 April 2016

The American Journal of Human Genetics

Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are associated with developmental delay, intellectual disability, and defects involving the brain, eye, ear, heart, and kidney. Arginine-glutamic acid dipeptide repeats (RERE) is located in the proximal 1p36 critical region. RERE is a widely-expressed nuclear receptor coregulator that positively regulates retinoic acid signaling. Animal models suggest that RERE deficiency might contribute to many of the structural and developmental birth defects and medical problems seen in individuals with 1p36 deletion syndrome, although human evidence supporting this role has been lacking. In this report, we describe ten individuals with intellectual disability, developmental delay, and/or autism spectrum disorder who carry rare and putatively damaging changes in RERE. In all cases in which both parental DNA samples were available, these changes were found to be de novo. Associated features that were recurrently seen in these individuals included hypotonia, seizures, behavioral problems, structural CNS anomalies, ophthalmologic anomalies, congenital heart defects, and genitourinary abnormalities. The spectrum of defects documented in these individuals is similar to that of a cohort of 31 individuals with isolated 1p36 deletions that include RERE and are recapitulated in RERE-deficient zebrafish and mice. Taken together, our findings suggest that mutations in RERE cause a genetic syndrome and that haploinsufficiency of RERE might be sufficient to cause many of the phenotypes associated with proximal 1p36 deletions.

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April 2016
16 Reads

Identification of critical regions and candidate genes for cardiovascular malformations and cardiomyopathy associated with deletions of chromosome 1p36.

PLoS One 2014 15;9(1):e85600. Epub 2014 Jan 15.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085600PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893250PMC
December 2014
40 Reads
9 Citations
3.234 Impact Factor

P2Y2 purinergic receptor activation is essential for efficient hepatocyte proliferation in response to partial hepatectomy.

Am J Physiol Gastrointest Liver Physiol 2014 Dec 9;307(11):G1073-87. Epub 2014 Oct 9.

Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Liver Center, Houston, Texas; Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas;

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http://ajpgi.physiology.org/content/ajpgi/307/11/G1073.full.
Web Search
http://ajpgi.physiology.org/content/ajpgi/early/2014/10/06/a
Web Search
http://ajpgi.physiology.org/cgi/doi/10.1152/ajpgi.00092.2014
Publisher Site
http://dx.doi.org/10.1152/ajpgi.00092.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254960PMC
December 2014
47 Reads
7 Citations
3.800 Impact Factor

P2Y2 purinergic receptor activation is essential for efficient hepatocyte proliferation in response to partial hepatectomy.

Am J Physiol Gastrointest Liver Physiol. 2014 Oct 9:ajpgi.00092.2014. doi: 10.1152/ajpgi.00092.2014

Am J Physiol Gastrointest Liver Physiol.

Abstract Extracellular nucleotides, via activation of P2 purinergic receptors, influence hepatocyte proliferation and liver regeneration in response to 70% partial hepatectomy (PH). Adult hepatocytes express multiple P2Y (G-protein coupled) and P2X (ligand-gated ion channels) purinergic receptor subtypes. However, the identity of key receptor subtype(s) important for efficient hepatocyte proliferation in regenerating livers remains unknown. In order to evaluate the impact of P2Y2 purinergic receptor-mediated signaling on hepatocyte proliferation in regenerating livers, wild type (WT) and P2Y2 purinergic receptor knockout (P2Y2-/-) mice were subjected to 70% PH. Liver tissues were analyzed for activation of early events critical for hepatocyte priming and subsequent cell cycle progression. Our findings suggest that early activation of p42/44 ERK MAPK (5 min), early growth response-1 (Egr-1), and activator protein-1 (AP-1) DNA-binding activity (30 min) as well as subsequent hepatocyte proliferation (24-72 hr) in response to 70% PH were impaired in P2Y2-/- mice. Interestingly, early induction of cytokines (TNFα, IL-6) and cytokine-mediated signaling (NF-kB, STAT-3) were intact in P2Y2-/- remnant livers, uncovering the importance of cytokine-independent and nucleotide-dependent early priming events critical for subsequent hepatocyte proliferation in regenerating livers. Hepatocytes isolated from WT and P2Y2-/- livers were treated with ATP for 5-120 min and 12-24 hr. Extracellular ATP alone, via activation of P2Y2 purinergic receptors, was sufficient to induce ERK phosphorylation, Egr-1 protein expression, and key cyclins and cell cycle progression of hepatocytes in vitro. Collectively, these findings highlight the functional significance of P2Y2 purinergic receptor activation for efficient hepatocyte priming and proliferation in response to PH. Copyright © 2014, American Journal of Physiology- Gastrointestinal and Liver Physiology. KEYWORDS: Extracellular ATP; P2Y2 purinergic receptors; hepatocyte proliferation; liver regeneration; partial hepatectomy PMID: 25301185 [PubMed - as supplied by publisher] Share on Facebook Share on Twitter Share on Google+

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October 2014
14 Reads

Novel frem1-related mouse phenotypes and evidence of genetic interactions with gata4 and slit3.

PLoS One 2013 11;8(3):e58830. Epub 2013 Mar 11.

Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058830PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594180PMC
December 2013
27 Reads
4 Citations
3.234 Impact Factor

PIAS1 is a GATA4 SUMO ligase that regulates GATA4-dependent intestinal promoters independent of SUMO ligase activity and GATA4 sumoylation.

PLoS One 2012 23;7(4):e35717. Epub 2012 Apr 23.

Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Michael E DeBakey VA Medical Center, Houston, Texas, United States of America.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035717PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334497PMC
September 2012
17 Reads
5 Citations
3.234 Impact Factor

Correction: PIAS1 Is a GATA4 SUMO Ligase That Regulates GATA4-Dependent Intestinal Promoters Independent of SUMO Ligase Activity and GATA4 Sumoylation

PLoS One. 2012;7(4):e35717. doi: 10.1371/journal.pone.0035717. Epub 2012 Apr 23.

PLoS ONE DOI: 10.1371/annotation/e56fbda3-1898-4a36-bf93-d33d5a8b2d2e

GATA4 confers cell type-specific gene expression on genes expressed in cardiovascular, gastro-intestinal, endocrine and neuronal tissues by interacting with various ubiquitous and cell-type-restricted transcriptional regulators. By using yeast two-hybrid screening approach, we have identified PIAS1 as an intestine-expressed GATA4 interacting protein. The physical interaction between GATA4 and PIAS1 was confirmed in mammalian cells by coimmunoprecipitation and two-hybrid analysis. The interacting domains were mapped to the second zinc finger and the adjacent C-terminal basic region of GATA4 and the RING finger and the adjoining C-terminal 60 amino acids of PIAS1. PIAS1 and GATA4 synergistically activated IFABP and SI promoters but not LPH promoters suggesting that PIAS1 differentially activates GATA4 targeted promoters. In primary murine enterocytes PIAS1 was recruited to the GATA4-regulated IFABP promoter. PIAS1 promoted SUMO-1 modification of GATA4 on lysine 366. However, sumoylation was not required for the nuclear localization and stability of GATA4. Further, neither GATA4 sumoylation nor the SUMO ligase activity of PIAS1 was required for coactivation of IFABP promoter by GATA4 and PIAS1. Together, our results demonstrate that PIAS1 is a SUMO ligase for GATA4 that differentially regulates GATA4 transcriptional activity independent of SUMO ligase activity and GATA4 sumoylation. DOI: 10.1371/journal.pone.0035717

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September 2012
17 Reads

Contribution of LPP copy number and sequence changes to esophageal atresia, tracheoesophageal fistula, and VACTERL association.

Am J Med Genet A 2012 Jul 25;158A(7):1785-7. Epub 2012 May 25.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

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http://dx.doi.org/10.1002/ajmg.a.35391DOI Listing
July 2012
39 Reads
6 Citations
2.160 Impact Factor

. Identification of a Novel Epidermal Growth Factor Receptor (EGFR) Binding Activity of Cyclin D1 Promoter During HepG2 Cell Proliferation and in Human Hepatocellular Carcinoma.

JOURNAL OF SURGICAL RESEARCH, Volume 151, Issue 2, February 2009, Pages 188-189. http://dx.doi.org/1

JOURNAL OF SURGICAL RESEARCH,

In hepatocellular carcinoma (HCC), overexpression of cyclin D1 (CD1) leads to unregulated growth. The specific transcription factors that activate the CD1 promoter have not been completely elucidated. Epidermal growth factor receptors (EGFRs) are expressed frequently in HCC and contribute to the aggressive growth of these tumors. Recent reports have shown that EGFRs may translocate to the nucleus and bind to AT-Rich motif sequences (ATRS), but this has not been previously reported in HCC. The purpose of this study was to investigate whether EGFRs translocate to the nucleus and interact with the CD1 promoter. Methods To explore if EGFR nuclear trafficking is regulated by EGF-induced phosphorylation, Western analysis was performed on cell extracts from HepG2, HepG3B, THLE-2 cells and samples obtained from patients with HCC using EGFR and pEGFR (Tyr1173) antibodies. Immunohistochemistry was also used to investigate EGFR nuclear protein expression in the transformed and cancer cell lines. To address the possibility of EGFR as a potential mediator of the observed increase in CD1 expression following EGF stimulation, the regulatory regions of the CD1 promoter were examined and we identified a 40-bp oligonucleotide sequence located at the 5' end of the CD1 promoter Region (CD1PR) encoding two consensus ATRS binding sites flanking an original TATA box-Inr element. To determine the EGFR binding activity of the CD1 promoter, electromobility shift assay (EMSA) was performed by incubating radiolabeled oligonucleotides representing the EGFR element of the CD1 promoter with the nuclear extracts obtained from the HepG2 cells that were grown to 70% confluence and from nuclear extracts obtained from patient HCC samples. The specificity of EGFR binding was confirmed by pre-incubating nuclear extracts with a 100-fold excess of specific (SP) and non-specific (NSP) cold competitors prior to the binding with labeled oligonucleotides. Chromatin immunoprecipitation assay (CHIP) was also performed to confirm binding of EGFR and pol II to the CD1PR in HepG2 cells and patient HCC samples. Results Western blot analysis from HCC specimens demonstrated increased EGFR protein levels in both cytoplasmic and nuclear fractions using wild type EGFR antibody. When pEGFR (Tyr1173) antibody was used, increased EGFR expression was demonstrated only in the nuclear fractions. Additionally, EGFR protein expression was significantly reduced in the cytoplasmic fraction obtained from HepG2 cells following EGF stimulation. Immunohistochemistry using the wild type EGFR antibody performed on THLE-2, Hep-3B and Hep-G2 cells demonstrated high protein expression in the cytoplasm in contrast to high levels in the nucleus when p-EGFR antibody was utilized. In HepG2 cells we demonstrate for the first time EGFR binding activity of the CD1 promoter. Correspondingly, there was increased EGFR binding activity of the CD1 promoter in samples obtained from patients with HCC. CHIP analysis also demonstrated specific DNA binding to the CD1PR for EGFR and pol II in HepG2 cells and HCC samples. Conclusion Our findings for the first time demonstrate that EGFR tyrosine-phosphorylation induces EGFR-nuclear localization and increased EGFR binding to a novel EGFR binding site in the CD1PR in HCC cells lines and HCC samples. Targeting EGFRs through inhibition of tyrosine-phosphorylation, EGFR nuclear trafficking, or its DNA binding activity may have potential therapeutic value in the treatment of HCC.

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February 2009
16 Reads

Serum lead, cadmium, and zinc levels in newborns with neural tube defects from a polluted zone in Mexico.

Reprod Toxicol 2004 Dec;19(2):149-54

Centro de Investigación Biomédica de la Universidad Autónoma de Coahuila, Biomedical Research Center at the Autonomous University of Coahuila, Mexico.

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http://dx.doi.org/10.1016/j.reprotox.2004.07.003DOI Listing
December 2004
23 Reads
3 Citations
3.230 Impact Factor

EFECTO DE LA PREINMUNIZACIÓN SOBRE LA EFICACIA TERAPÉUTICA Y TOXICIDAD DE LA TERAPIA GÉNICA ANTITUMORAL

CIENCIA UANL 10/2003; VOL. VI,(No. 4, OCTUBRE-DICIEMBRE 2003):497-507.

CIENCIA UANL

ABSTRACT: Los adenovirus recombinantes de origen humano se utilizan ampliamente en protocolos de terapia génica, tanto en modelos preclínicos como en estudios clínicos en fase I. Su explosiva utilización se debe, en parte, a que los vectores adenovirales de primera generación exhiben una notable y prolongada estabilidad biológica dentro del torrente circulatorio. Esta condición les permite funcionar como excelentes vehículos que transportan genes terapéuticos a varios órganos, diferentes tumores y a diversos tipos de células neoplásicas. A pesar de esta ventaja biológica, existen dos importantes factores que han limitado que se explote el potencial de los vectores adenovirales en protocolos de terapia génica. El primer problema es su carencia de especificidad hacia un solo tipo de células huésped. En efecto, los adenovirus pueden infectar un amplio rango de líneas celulares, lo cual hace difícil restringir el transporte de genes terapéuticos por vía endovenosa hacia un determinado grupo de células o hasta un órgano en particular.1,2 Una segunda desventaja, observada durante el uso de adenovirus en el tratamiento del cáncer, es el desarrollo de una respuesta inmunológica en contra de las partículas virales dentro del paciente.3,4,5 Durante un ciclo inicial de tratamiento, tales vectores pueden infectar un número apropiado de células y producir una alta expresión de la proteína deseada. Pero pronto las respuestas celular y humoral desarrolladas por el paciente interferirán con la expresión del gen terapéutico, y resultarán en la aparición de fenómenos de citotoxicidad.6,7,8,9 Desde otra perspectiva, la presencia de anticuerpos circulantes en contra de adenovirus pudiera ejercer un efecto protector en los tejidos normales y reducir el riesgo de complicaciones, transformándose así en un factor de bioseguridad, ya que permitiría administrar dosis masivas de adenovirus por vía intratumoral, sin la diseminación consecuente del vector, garantizando una elevada expresión y persistencia de los genes terapéuticos. Esta situación se torna especialmente importante después de la muerte de Jesse Gelsinger, afectado por una enfermedad metabólica conocida como deficiencia de Ornitin Transcarbamilasa (OTC). Jesse desarrolló un síndrome de distrés respiratorio del adulto (SDRA) complicado con falla orgánica múlti ple (FOM), mientras participaba en un protocolo de terapia génica diseñado por la Universidad de Pennsylvania. El protocolo fase I en cuestión consistió en inocular una sola dosis (6 X 1011 partículas/Kg) de un adv-vector (H5.001CBhOTC) que expresa el ADNc que codifica para la enzima OTC en la arteria hepática derecha del paciente. Después de este reporte los Institutos Nacionales de Salud (NIH) revisaron los efectos adversos de los adenovirus en macacos, encontrando que todos los simios inoculados con este tipo de vectores desarrollaron fenómenos de hepatotoxicidad y se reportaron severamente enfermos, este hecho, aunado con el conocimiento de que los 18 pacientes pertenecientes al protocolo OTC de la Universidad de Pennsylvania presentaron titulaciones elevadas de anticuerpos neutralizantes en contra del vector H5.001CBhOTC,10 obligó a la Federal Drug Administration de EUA a suspender todos los estudios de terapia génica que se llevaban a cabo en dicha Universidad. El informe final de este organismo destacó que: Jesse Gelsinger sufrió una activación difusa de su sistema inmune tras la inyección del vector, como consecuencia de ello desarrolló los síndromes de SDRA y FOM. En el presente trabajo, utilizamos un modelo murino preinmunizado a través de la inyección intratumoral (IT) de adenovirus, para investigar la posible participación del sistema inmune en la transferencia génica mediada por adv-vectores en el tratamiento de tumores sólidos. La preinmunización provocó un incremento en la titulación de anticuerpos antiadenovirus que ocasionó una disminución en los niveles de transferencia y expresión génica. Los aspectos de toxicidad sistémica fueron determinados por medio de estudios enzimáticos e histológicos. El establecimiento de una respuesta humoral contra adenovirus redujo significativamente la transducción sistémica con el vector. Sin embargo, dicha reducción no se tradujo en un efecto protector en los tejidos normales. Paradójicamente, la respuesta inmune montada en contra del vector resultó en un incremento de los parámetros de toxicidad hepática comparados con los observados en animales controles.

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October 2003
14 Reads

[Genetic therapy of cancer].

Rev Invest Clin 2002 Jan-Feb;54(1):57-67

Laboratorio de Genética Molecular, Unidad de Laboratorios de Ingeniería y Expresión Genéticas, Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, N.L., México.

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June 2002
30 Reads

[The Mexican experience of social service in medicine. Perspectives on an ongoing effort].

Educ Med Salud. 1994 Jul-Sep;28(3):341-54.

Educ Med Salud. 1994 Jul-Sep;28(3):341-54.

ABSTRACT: En México, el servicio social en medicina es una actividad que se lleva a cabo a través de la concertación entre diferentes sectores e instituciones. Consiste fundamentalmente en la atención médica que los egresados de las escuelas y facultades de medicina del país (médicos pasantes) proporcionan. Este servicio se dirige a la población que por sus características geográficas, económicas y sociales presenta limitaciones en cuanto al acceso a los servicios públicos, la educación, la vivienda y la alimentación, entre otros. La conceptualización del servicio social incluye en sí aspectos de tipo social, académico y legal que se realizan de acuerdo con un programa de actividades asistenciales estructurado y dirigido por la Secretaría de Salud, dentro del marco que proporciona el Programa Nacional de Salud. Esta atención se ofrece también en concordancia con un programa académico exprofeso para este fin, responsabilidad legal de las instituciones académicas de procedencia de los médicos pasantes. El aspecto legal del sevicio social lo constituye el requisito que deben cumplir los egresados de la carrera de medicina para obtener su título profesional y, de esa manera, obtener también el registro para su ejercicio ante la Dirección General de Profesiones de la Secretaría de Educación Pública. En México, el servicio social en medicina ha representado históricamente un medio de concertación que, encabezado por el Estado, articula las actividades de los sectores educativo y asistencial, dentro de su propio marco legal. Esta articulación es posible gracias al profundo carácter social de las instituciones educativas y asistenciales. La orientación social proviene de dos fuentes: la filosofía social emanada de la ideología de la Revolución Mexicana y los lineamientos generales del modelo de Estado de Bienestar, Welfare State, configurado en los Estados Unidos de América y proyectado a nivel internacional desde la década de 1930. Dentro de esta filosofía social se anudan los lazos que sostienen el servicio social médico en México.

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July 1994
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Induction of sister-chromatid exchanges in Vicia faba by arsenic-contaminated drinking water.

Mutat Res. 1988 Jul;208(3-4):219-24.

Mutation Research

Abstract Arsenic-contaminated drinking water from various towns of Comarca Lagunera, Coahuila, Mexico, was tested for its ability to induce sister-chromatid exchanges (SCE) in Vicia faba. 3-h treatments were applied and the differential staining technique of Tempelaar et al. (1982) was used. Atomic absorption spectrophotometry showed that the arsenic concentration in drinking water was 0.11-0.695 ppm, well over the maximum limit of 0.05 ppm (EPA, 1984). In all cases the SCE frequencies were significantly different from the controls. Some concentrations (0.2, 0.3, 0.5 and 1.0 ppm) of sodium arsenate (V) and potassium arsenite (III) were also applied to Vicia faba and all produced significant SCE frequencies, except 0.2 ppm of sodium arsenate.

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July 1988
15 Reads

Gerodermia osteodysplastica hereditaria: report of three affected brothers and literature review.

Am J Med Genet. 1979;3(4):389-95.

American Journal of Medical Genetics.

Abstract Gerodermia osteodysplastica hereditaria was diagnosed in three Mexican brothers 6, 7, and 8 years old, respectively, who had the distinct facial appearance with sagging cheeks, premature wrinkling of the skin of face, abdomen, and dorsum of hands and feet; malocclusion, span greater than height; hyperextensibility; winging of the scapulae; stooped posture with kyphoscoliosis; protuberant abdomen; and pes planus. Radiologically they had generalized osteoplorosis, platyspondily due to multiple compression fractures, pseudoepiphyses of second metacarpals, and dislocated hips. Three other families with a total of 14 affected individuals have been reported. Inter- and intrafamilial variability can be recognized, particularly regarding the tendency to fractures, upper:lower segment ratio abnormalities, and results of skin biopsies, which have shown fragmentation of the elastic fibers in some cases (including the present family) and not in others. Although inheritance was considered to be X-linked recessive in the first reported family, an analysis of that pedigree together with those of the other reported families, including the present one, suggests that gerodermia osteodrysplastica is inherited in an autosomal recessive manner.

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March 1979
12 Reads

Peroxisomal proliferation induced by treatment with clofibrate in a patient with a peroxisomal disease.

Cell Biochemistry and Biophysics 02/2000; 32 Spring:329-32. DOI:10.1385/CBB:32:1-3:329 ·

Cell Biochemistry and Biophysics

ABSTRACT: The induction of peroxisomal proliferation in liver parenchymal cells of rats fed a diet containing clofibrate, a hypolipidemic drug, is a well-established event. However, the available data on human hepatocytes in vivo and in vitro indicate that agents that induce peroxisomal proliferation in rats and mice have no effect on human liver cells. The authors are reporting the case of a patient with clinical and laboratory diagnosis of X-linked-adrenoleukodystrophy. In an initial liver biopsy, a reduced volume fraction of peroxisomes was found (Vv. = .012) after a morphometric analysis, initiating treatment with clofibrate at a dose of 1.5 g/d. The administration of clofibrate was maintained for 7 yr. Liver biopsies were taken after 2, 4, and 7 yr, to follow the peroxisomal response. Results demonstrated a 500% increase in peroxisomal Vv. (.060) after 2 yr of treatment, compared with the pretreatment Vv. In subsequent biopsies, the peroxisomal Vv. value was maintained at 225 and 183% increases above the pretreatment biopsy (.027 and .022, respectively).

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17 Reads

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Daryl A Scott

Baylor College of Medicine

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BAYLOR COLLEGE OF MEDICINE

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Kangnam Sacred-Heart Hospital

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Tyler F Beck

Baylor College of Medicine

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Baylor College of Medicine

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Valerie K Jordan

Baylor College of Medicine

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James R Lupski

Baylor College of Medicine

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Seema R Lalani

Baylor College of Medicine

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Brendan Lee

Baylor College of Medicine

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Zhiyin Yu

State Key Laboratory of Phytochemistry and Plant Resources in West China

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