Principal Investigator/Program Director (Last, first, middle):
Hu, Chien-An A.
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel in the order listed for Form Page 2.
Follow this format for each person. (See attached sample.) DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Chien-An A. Hu, Ph.D.
Vice Chair & Associate Professor, Biochemistry and
Molecular Biology
eRA COMMONS USER NAME (credential, e.g., agency login)
PSALM23
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
Soochow University, Taipei, Taiwan
The Ohio State University, Columbus, OH
The Ohio State University, Columbus, OH
Johns Hopkins Medical Institutes, Baltimore, MD
DEGREE
(if applicable)
B.S.
M.S.
Ph.D.
Post-Doc
YEAR(s)
1985
1990
1992
1993-1997
FIELD OF STUDY
Microbiology
Molecular Genetics
Molecular Genetics
Human Molecular
Genetics
NOTE: The Biographical Sketch may not exceed four pages. Items A and B may not exceed two of the fourpage limit.
A. Personal Statement. Dr. Hu was trained as a human geneticist and biochemist at Johns Hopkins Medical
Institutes and have published peer-reviewed papers in inborn errors of metabolism, ROS stress and
programmed cell death (both apoptosis and autophagy) in human cancer. In 2004, his laboratory pioneered the
cloning and characterization of human apolipoprotein L6 (ApoL6), which, when overexpressed, induced
mitochondria-mediated apoptosis in cancer cells. In addition, they also identified and characterized ApoL1,
another member of the same family, which induces autophagy and Atg5 and Atg7-dependent cell death. Dr.
Hu’s team has recently demonstrated that ApoL6 is one of the downstream targets of interferon-sensitized,
Fas-induced apoptosis in cnacer cells, and is a causal factor regulating both mitochondria-mediated apoptosis
and Beclin 1-dependent autophagy. His group will continue dissect the molecular basis of ApoL6- and ApoL1regulated apoptosis and autophagy in cell models of renal cell crcinoma and prostate cancer.
B. Positions and Honors. List in chronological order previous positions, concluding with your present position. List
any honors. Include present membership on any Federal Government public advisory committee.
2010Vice Chairman, Department of Biochemistry & Molecular Biology, UNM SOM
2006Associate Professor, Department of Biochemistry & Molecular Biology, UNM SOM
2001-2006 Assistant Professor, Department of Biochemistry & Molecular Biology, University of New
Mexico, School of Medicine (UNM SOM)
1997-2001 Research Faculty, Department of Pediatrics, Johns Hopkins Medical Institutes
1993-1997 Postdoctoral Research Associate, Howard Hughes Medical Institute and Program in Human
Genetics and Molecular Biology and Department of Pediatrics, Johns Hopkins Medical Institutes
1987-1993 Graduate Teaching Assistant, Department of Molecular Genetics, The Ohio State University,
Columbus, OH
1985-1987 Military Technician, Clinical Laboratory, Naval General Hospital, Taiwan
1983-1985 Undergraduate Research Assistant, Department of Microbiology, Soochow University, Taiwan
Honors and Awards
2006&2009 AACR Minority-Serving Institution Faculty Scholar Award in Cancer Research
2001
American Cancer Society Institutional Grant at UNM-HSC. Twice invited to speak to cancer
survivors, volunteers and fund raisers in “Relay for Life 2002, American Cancer Society” at
Los Alamos and Hobbs, 2002.
1997
Francis F. Schwentker Award for Excellence in Research by Residents and Fellows,
Department of Pediatrics, Johns Hopkins Hospital
1993-1997 Howard Hughes Medical Institute Postdoctoral Fellowship
1992
Outstanding Research Paper Award, 1992 Graduate Research Forum in the Area of
Biological Sciences, Council of Graduate Students, The Ohio State University
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Principal Investigator/Program Director (Last, first, middle):
1992
1985
Hu, Chien-An A.
Scott Falkenthal Memorial Graduate Student Colloquium Award, Department of Molecular
Genetics, The Ohio State University
Undergraduate Thesis Award, Department of Microbiology, Soochow University
C. Selected peer-reviewed publications since 2001 (in reverse chronological order). (selected from more than 30 peer
reviewed papers)
1.
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3
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5
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14.
15.
Kaini, RR, Sillerud, LO, Zhaorigetu, S, Hu, CA. Autophagy regulates lipolysis and cell survival through
lipid droplet degradation in androgen-sensitive prostate cancer cells. Prostate. 2012 Jan 31. doi:
10.1002/pros.22489. [Epub ahead of print] PubMed PMID: 22294520.
Zhaorigetu S, Yang Z, Toma I, McCaffrey TA, Hu, CA. Apolipoprotein L6, induced in atherosclerotic
lesions, promotes apoptosis and blocks Beclin 1-deependent autophagy in atherosclerotic cells. J Biol
Chem. (2011) 286:27389-27398.
Zhaorigetu S, Wan G, Kaini R, Jiang Z, Hu CA. ApoL1, a BH3-only lipid-binding protein, induces
autophagic cell death. Autophagy. (2008) 4: 1079-1082.
Hu CA, Williams DB, Zhaorigetu S, Khalil S, Wan G, Valle D. Functional genomics and SNP analysis of
human genes encoding proline metabolic enzymes. Amino Acids. (2008) 35: 655-664.
Hu CA, Khalil S, Zhaorigetu S, Liu Z, Tyler M, Wan G, Valle D. Human Delta(1)-pyrroline-5-carboxylate
synthase: function and regulation. Amino Acids. (2008) 35: 665-672.
Wan G, Zhaorigetu S, Liu Z, Kaini R, Jiang Z, Hu CA. Apolipoprotein L1, a novel BH3-only lipid binding
protein, induces autophagic cell death. J Biol Chem. (2008) 283:21540-21549.
Liu Z, Wan G, Heaphy C, Bisoffi M, Griffith JK, Hu CA. A novel loss-of-function mutation in TP53 in an
endometrial cancer cell line and uterine papillary serous carcinoma model. Mol Cell Biochem. (2007)
297:179-187.
Hu CA, Donald SP, Yu J, Lin WW, Liu Z, Steel G, Obie C, Valle D, Phang JM. Overexpression of
proline oxidase induces proline-dependent and mitochondria-mediated apoptosis. Mol Cell Biochem.
(2007) 295:85-92.
Liu Y, Borchert GL, Surazynski A, Hu CA, Phang JM. Proline oxidase activates both intrinsic and
extrinsic pathways for apoptosis: the role of ROS/superoxides, NFAT and MEK/ERK signaling.
Oncogene. (2006) 25:5640-5647.
Liu Y, Borchert GL, Donald SP, Surazynski A, Hu CA, Weydert CJ, Oberley LW, Phang JM. MnSOD
inhibits proline oxidase-induced apoptosis in colorectal cancer cells. Carcinogenesis. (2005) 26:13351342.
Bender HU, Almashanu S, Steel G, Hu CA, Lin WW, Willis A, Pulver A, Valle D. Functional
consequences of PRODH missense mutations. Am J Hum Genet. (2005) 76:409-420.
Liu Z, Lu H, Shi H, Du Y, Yu J, Gu S, Chen X, Liu KJ, Hu CA. PUMA overexpression induces reactive
oxygen species generation and proteasome-mediated stathmin degradation in colorectal cancer cells.
Cancer Res. (2005) 65:1647-1654.
Liu Z, Lu H, Jiang Z, Pastuszyn A, Hu CA. Apolipoprotein L6, a novel proapoptotic Bcl-2 homology 3only protein, induces mitochondria-mediated apoptosis in cancer cells. Mol Cancer Res. (2005) 3:2131.
Gu S, Du Y, Chen J, Liu Z, Bradbury M, Hu CA, Chen X. (2004) Large-scale quantitative proteomic
study of PUMA-induced apoptosis using two-dimensional liquid chromatography-mass spectrometry
coupled with amino acid-coded tagging. J. Proteome Res. 3, 1191-1200.
Gu S, Liu Z, Pan S, Jiang Z, Lu H, Amit O, Bradbury EM, Hu CA, Chen X. Global investigation of p53induced apoptosis through quantitative proteomic profiling using comparative amino acid-coded
tagging. Mol Cell Proteomics. (2004) 3:998-1008.
D. Research Support. List selected ongoing or completed (during the last three years) research projects (federal and
non-federal support). Begin with the projects that are most relevant to the research proposed in this application.
Briefly indicate the overall goals of the projects and responsibilities of principal investigator identified above.
Current
Project title: “High-Throughput Screening of Repurposing Drugs in Blocking ApoL6-induced Apoptosis in
Atherosclerosis”
Principal investigator: HU, Chien-An A.
Percent effort: 3%
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Principal Investigator/Program Director (Last, first, middle):
Hu, Chien-An A.
Funding organization: UNM HSC
Starting and stopping dates: October 1, 2011-September 30, 2012
Amount awarded for the period listed:
Direct costs: $24,000
Summary: High-throughput screening of repurposing drugs in the Prestwick library in blocking ApoL6induced apoptosis using DLD-1.ApoL6 cell line as a cell-based system.
Project title: “Role of ApoL6 in atherosclerosis”
Principal investigator: HU, Chien-An A.
Percent effort: 5%
Funding organization: UNM HSC
Starting and stopping dates: April 1, 2010-December 31, 2012
Amount awarded for the period listed:
Direct costs: $65,000
Summary: To investigate the function of ApoL6 in ROS generation and apoptosis in atherosclerosis.
Project title: “The combined structural bioinformatics and functional approach for the characterization of
the nonsynonymous SNPs of apolipoprotein Ls (ApoLs)”
Principal investigator: HU, Chien-An A. (Task #7)
Percent effort: 5%
Funding organization: New Mexico INBRE (2P20RR016480); Dr. Jeffrey B. Arterburn, P.I., New
Mexico State University
Starting and stopping dates: July 2009-April 2014
Amount awarded for the period listed:
Direct costs: $18,000/yr; indirect costs: ~$ 9,000/yr
Summary: To dissect functions of the nonsynonymous SNP alleles of ApoLs using structural and
functional analysis.
Pending:
Project title: “The Role and Blocking of ApoL6-induced Apoptosis in Atherosclerosis”
Principal investigator: HU, Chien-An A.
Percent effort: 40%
Funding organization: NIHLB Multi-PI RO1 (1RO1HL114693-01)
Starting and stopping dates: April 01, 2012-March 31, 2017
Amount requested for the period listed:
Direct costs: $425,000/year; indirect costs: ~$ 215,000/year
Previous:
Project title: “Novel proapoptotic BH3-only proteins in cancer apoptosis”
Principal investigator: HU, Chien-An A.
Percent effort: 40%
Funding organization: NCI RO1 (5RO1CA106644)
Starting and stopping dates: May 15, 2005-March 31, 2010; no cost extension until March 31, 2011
Amount awarded for the period listed:
Direct costs: $150,000/year; indirect costs: ~$ 75,000
Summary: Using a combination of sophisticated approaches in database mining, functional genomics,
structural prediction, proteomics, lipidomics, and functional assays, this project aims at the identification
and characterization of novel BH3-only pro-death genes/proteins and their roles in cancer cell death.
Project title: “Molecular basis of autophagic cell death in prostate cancer”
Principal investigator: HU, Chien-An A.
Percent effort: 3%
Funding organization: DOD PCRP (PC074041; W81XWH-08-1-0183)
Starting and stopping dates: March 1, 2008-April 30, 2011
Amount awarded for the period listed:
Direct costs: $99,900 total; indirect costs: $7,992
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Principal Investigator/Program Director (Last, first, middle):
Hu, Chien-An A.
Summary: A pre-doctoral training grant for Dr. Ramesh Kaini, MD, to conduct research on the
molecular basis of autophagy in prostate normal and cancerous cells as a PhD project.
Project title: “Functions of apolipoproteins in programmed cell death”
Principal investigator: HU, Chien-An A. (one of the 19 investigators in this state-wide project)
Percent effort: 15%
Funding organization: New Mexico INBRE (2P20RR016480-04); Dr. Jeffrey B. Arterburn, P.I., New
Mexico State University
Starting and stopping dates: July 2004-April 2009
Amount awarded for the period listed:
Direct costs: $75,000/yr; indirect costs: ~$ 37,000/yr
Summary: To study the molecular bases of programmed cell death, both apoptosis and autophagy, that
are induced by apolipoprotein L (ApoL) family members, L1-L6, in cancer and other diseases.
Project title: “Mutations of PUMA cause prostate cancer development and aggressiveness”
Principal investigator: HU, Chien-An A.
Percent effort: 17%
Funding organization: Department of Army (PC040298; W81XWH-05-1-0357)
Starting and stopping dates: May 2005-May 2007
Amount awarded for the period listed:
Direct costs: $73,833/total; indirect costs: $ 18,890/total
Summary: Based on our preliminary observation that expression of PUMA (P53 Upregulated
Modulator of Apoptosis) is relatively high in normal prostate cells and significantly reduced in prostate
cancer (PCa) cell models, and the fact that PUMA’s chromosome localization on 19q13 and PUMA’s
role as a pro-apoptotic effector, we hypothesized that PUMA may be a candidate gene (or susceptibility
locus) that, when mutated or downregulated, promotes tumor progression and aggressiveness.
Moreover, based on the strong familial linkage between chromosome 19q13 and PCa in different
families, and the availability of DNA samples from PCa patients, we further hypothesized that there may
be some pathological point-mutation or small-deletion mutant alleles of PUMA that were inherited in the
chromosome 19q13-associated PCa families. In this project, we (1) surveyed the PUMA gene for
mutations using RT-PCR amplification, PCR amplification of genomic DNA and direct sequencing of
amplified amplicons from PCa cell models, LNCaP, DU145 and PC3; and (2) surveyed the PUMA gene
for mutations using PCR amplification of genomic DNA and direct sequencing of amplified amplicons of
the clinical samples that were isolated from PCa patients and control. We found no mutations in the
coding sequence of PUMA gene of the familial, 19q13-associated PCa patients. It is possible that
PUMA in not “the gene” mutated in 19q13-associated PCa patients. This notion is supported by three
recent papers documenting that the coding sequence of PUMA is not mutated in three other cancer
types, gastric, colorectal and head and neck. Alternatively, mutations could be present in the 5’-UTR,
promoter region or introns of PUMA gene.
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