Download BIOGRAPHICAL SKETCH A. Personal Statement

BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME: Pineda, Gabriel
eRA COMMONS USER NAME (agency login): GPINEDA
POSITION TITLE: Assistant Project Scientist
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
include postdoctoral training and residency training if applicable.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
University of Texas at Austin, Austin, TX
BS
University of Texas at El Paso, El Paso, TX
MS
University of Texas Southwestern Medical Center at PHD
Dallas, Dallas, TX
St. Elizabeth School of Medical Technology,
Other training
Beaumont, TX
Marine Biological Laboratory, Woods Hole, MA,
Other training
Woods Hole, MA
University of California, San Diego, San Diego, CA
Other training
University of California, San Diego, Moores Cancer
Postdoctoral
Center, San Diego, CA
Fellow
University of California, San Diego, Sanford
Postdoctoral
Consortium for Regenerative Medicine, San Diego, CA Fellow
Completion
Date
MM/YYYY
08/1998
12/2001
05/2008
FIELD OF STUDY
08/1999
Microbiology
Molecular Biology
Biochemistry-Ubiquitination,
Innate Immunity
Medical Technology
08/2002
Physiology Course
03/2011
09/2011
Clinical Research Certificate
Cancer Biology
09/2014
Cancer Stem Cell Biology
A. Personal Statement
Proposal Goal - The ultimate goal of the proposed research is to understand how WNT mediated signaling
regulates survival and self-renewal in acute myeloid leukemia (AML) stem cells. The knowledge gained from
these studies will elucidate molecular mechanisms that will be exploited to identify new therapeutic targets to
treat AML.
Relevant Experiences - My research background and experience in molecular biology, biochemistry, cancer
biology, clinical research, and cancer stem cell biology have prepared me for a career in the translational
cancer research field. From my Ph.D. training in biochemistry under the mentorship of HHMI investigator Dr.
Zhijian J. Chen, my postdoctoral training in the distinguished laboratory of cancer biologist Dr. Jean Wang, and
renowned cancer stem cell biologist Dr. Catriona Jamieson I believe I have mastered the foundation to be an
independent scientist who can perform hypothesis-driven translational research. My doctoral work at UT
Southwestern Medical Center at Dallas biochemically elucidated how the post-translational modification by
ubiquitin leads to activation or inhibition of NF-κB signaling in human cancer cells. I was trained to decipher
cell-signaling events in cancer cells by utilizing in vitro cell free systems to recapitulate and define molecular
mechanisms. From my postdoctoral training in cancer biology in the distinguished lab of Dr. Jean Wang at the
University of California, San Diego, we discovered, developed, and validated a proteomic approach to study
the interactome of RNA polymerase II C-terminal repeated domain. To compete these studies I successfully
collaborated with other preeminent researchers in the fields of phospho and functional proteomics. During
2009-2011 my career was disrupted due to obligations required to cope with a family illness. However, during
this time I generated a substantial amount of data that has resulted in one first author manuscript that was
recently revised and submitted to the peer-reviewed journal BMC Research Notes entitled “Proteomics Studies
of the Interactome of RNA Polymerase II C-Terminal Repeated Domain” concluding my collaborative studies
on the CTD code and how the CTD phosphorylation code can be regulated by DNA damage. Results from
these studies provided the basis for successful application to obtain Recovery Act funds (NOT-OD-09-058). I
also successfully completed all classwork to obtain a CREST certificate in clinical research. In my postdoctoral
training in cancer stem cell biology in the laboratory of Dr. Catriona Jamieson at the University of California,
San Diego, I have gained training in methods used to study leukemia stem cell (LSC) biology. My current
studies involve understanding which pathways promote dormant human leukemia stem cell generation. My
contribution and collaboration on the studies of the deregulation of hedgehog (Hh) signaling were published in
the Journal of Translational Medicine. This publication is evidence that I have successfully managed to
translate preclinical discoveries to establish new therapeutic options for patients with cancer. I recently have
submitted a manuscript to Nature Methods entitled “Real-time Live Single Normal and Malignant Progenitor
Cell Cycle Transit Time Tracking in a Defined Niche” describing my studies of cell cycle kinetics and gene
expression profiles of leukemic progenitors on a defined niche using a lentiviral bicistronic Fucci2BL reporter I
developed.
Leadership Qualifications - From these experiences it is clear I have a pension to establish innovative methods
to generate high impact discoveries. I am now poised to make translational discoveries that will make a direct
contribution to human health. In summary, my mentor and I have a demonstrated record of accomplished and
productive research projects in areas of high relevance for our proposed research. My expertise and
experience have prepared me to lead the proposed project.
1. Sadarangani A, Pineda G, Lennon KM, et. al. (2015) GLI2 inhibition abrogates human leukemia stem
cell dormancy. J Transl Med, 13(98). (PMID:25889765)
B. Positions and Honors
Positions and Employment
1998 - 1999
1998 - 1999
1999 - 2000
2000 - 2001
2000 - 2001
2001 - 2008
2008 - 2011
2010 - 2011
2011 - 2012
2012 - 2014
2012 - 2014
2014 -
Medical Technology Student, St. Elizabeth Hospital, Beaumont, TX
Phlebotomist/Assistant Diener/Lab Technician , St. Elizabeth Hospital, Beaumont, TX
Medical Technologist, Providence Memorial Hospital, El Paso, TX
Master's Graduate Student, University of Texas at El Paso, El Paso, TX
Graduate Teaching Assistant, University of Texas at El Paso, El Paso, TX
Doctoral Graduate Student, UT Southwestern, Zhijian J. Chen Lab, Dallas, TX
Postdoctoral fellow-Jean Wang Lab, University of California, San Diego, San Diego, CA
Lecturer, San Diego State University, San Diego, CA
Scientist, GenWay Biotech Inc., San Diego, CA
Lecturer, San Diego State University, San Diego, CA
Postdoctoral fellow, University of California, San Diego, Jamieson Lab, San Diego, CA
Assistant Project Scientist, University of California, San Diego, Jamieson Lab, San Diego, CA
Other Experience and Professional Memberships
2014 2014 -
Associate Member, American Association for Cancer Research
Member, American Society for Cell Biology
Honors
1994
2000
2000
2000
2000
2001
2002
2002
2002
2002
SUCCESS Scholarship, University of Texas at Austin
Graduate Professional Funding, University of Texas as El Paso
Travel Award for Genetic Education for Native Americans Workshop, SACNAS
Travel Award for 40th Annual ASCB Meeting, American Society for Cell Biology, MAC
Travel Award for SACNAS Annual Conference, SACNAS
First Place Poster at ASM Regional Conference, American Society of Microbiology Rio Grande
Branch
William Townsend Porter Scholarship to attend Physiology course at Marine Biological
Laboratory, William Townsend Porter Foundation
Scholarship from Division of Cellular and Molecular Biology to attend Physiology course at
Marine Biological Laboratory, UT Southwestern
Invited Seminar Speaker, University of Texas at El Paso
Scholarship to attend Physiology course at Marine Biological Laboratory, American Society for
2008
2010
2012
2012
2013
2014
Cell Biology, MAC
CREST Scholar , Clinical Research Enhancement through Supplemental Training, University of
California, San Diego
Carl Storm URM Fellowship, Gordon Research Conference
Mountain West Summer Institute Fellow, HHMI / National Academy of Sciences
Invited Seminar Speaker , California State University Northridge
Mountain West Summer Institute Alumni Fellow, HHMI / National Academy of Sciences
AACR Minority Scholar in Cancer Research Award, AACR
C. Contribution to Science
1. For years the emphasis of studying the function of ubiquitination focused on how this post-translational
modification regulated protein turnover through proteosomal dependent degradation. The tagging of
proteins with lysine-48 linked ubiquitin chains is responsible for proteasomal degradation. In the following
studies I made significant contributions by establishing an in vitro cell free system to analyze how lysine-63
linked ubiquitination regulated NF-KappaB activation. In particular I established an assay using highly
purified recombinant proteins to study the isopeptidase activity of CYLD a lysine-63 specific deubiquitinase.
This enzyme is a very useful tool used to help confirm free lysine-63 linked ubiquitin chains can activate
IKK. I also contributed to generating mutants and stable cells lines used to study how NEMO ubiquitin
binding leads to the activation IKK.
a. Ea CK, Deng L, Xia ZP, Pineda G, Chen ZJ. Activation of IKK by TNFalpha requires site-specific
ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell. 2006 Apr 21;22(2):245-57.
PubMed PMID: 16603398.
b. Pineda G, Ea CK, Chen ZJ. Ubiquitination and TRAF signaling. Adv Exp Med Biol. 2007;597:80-92.
PubMed PMID: 17633019.
c. Xia ZP, Sun L, Chen X, Pineda G, Jiang X, Adhikari A, Zeng W, Chen ZJ. Direct activation of protein
kinases by unanchored polyubiquitin chains. Nature. 2009 Sep 3;461(7260):114-9. PubMed PMID:
19675569; PubMed Central PMCID: PMC2747300.
2. It had been shown that the hepatitis C protease NS3/4A could negatively regulate interferon in infected
mammalian cells. The mechanism of this inhibition had not been known until our work identified the protein
MAVS as the substrate and target of the NS3/4A proteases. MAVS is a key activator of interferon signaling
in the cell. Specifically my contribution to the work was to determine levels of interferon activated target
genes by QPCR in cells overexpressing NS3/4A and to generate a panel of MAVS mutants used to identify
key domains required for inhibition by MAVS.
a. Li XD, Sun L, Seth RB, Pineda G, Chen ZJ. Hepatitis C virus protease NS3/4A cleaves mitochondrial
antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci U S A.
2005 Dec 6;102(49):17717-22. PubMed PMID: 16301520; PubMed Central PMCID: PMC1308909.
D. Research Support
Completed Research Support
2012/07/01-2014/06/01
K12GM068524, NIH/NIGMS IRACDA
JoAnn Trejo (PI)
Wnt Mediated Regulation of ROR1 Signaling in Acute Myeloid Leukemia
Role: Post-Doctoral Scholar
2011/08/01-2012/09/30
K12GM068524, NIH/NIGMS IRACDA
Laurence Brunton (PI)
Proteomics Studies of the Interactome of RNA Polymerase II C-Terminal Repeated Domain
Role: Post-Doctoral Scholar
2009/09/01-2011/09/01
CA043054, National Cancer Institute
Jean Y.J. Wang (PI)
Nuclear Function of Abl in DNA Damage Response
Role: KP
2008/07/01-2011/07/01
T32CA121938, National Cancer Institute
Pineda, Gabriel (PI)
Proteomics Studies of the Interactome of RNA Polymerase II C-Terminal Repeated Domain
Role: Post-Doctoral Scholar
2003/08/01-2007/08/20
F31GM068979, NIH/NIGMS
Pineda, Gabriel (PI)
NF-Kappa B Signaling Pathway & Ubiquitin Proteasome Degradation Pathway
Role: GR