Hinh Ly, PhD

Cancer Biology
Microbial Pathogenesis

Assistant Professor
Pathology & Laboratory Medicine

Other Appointments/Positions

Member of Strategic Planning Cmte, WCI Cancer Genetics and Epigenetic Program

Training Faculty Member, Postdoctoral Fellowships in Research & Science Teaching (FIRST) Program

Member, Emory Center for Environmental Health Sciences

Member, GMB Executive Committee and Recruitment Committee

Member, Emory Digestive Diseases Research & Development Center

Training Faculty Member, Genetics & Mol. Biol. (GMB) Graduate Training Program

Training Faculty member, Immunology & Mol. Pathogenesis (IMP) Graduate Training Program

Pathology Division(s):
Experimental Pathology

Email Address:
hly@emory.edu

Education:

B.S. & M.A.   Univ. of Calif. Los Angeles (UCLA), Microbiology & Molecular Genetics (Advisors: Bob Simons & Don Nierlich), - 1998

Ph.D.   Univ. of North Carolina at Chapel Hill (UNC), Microbiology & Immunology (Advisor: the late Andy Kaplan), - 2000

Postdoctoral fellowship   Univ. of Calif., San Francisco (UCSF), Microbiol. & Immunol. and Pathology (Advisors: Liz Blackburn & Tris Parslow), - 2003

Research Interests:

- Role of telomere-telomerase biology in the pathogenesis of human bone-marrow failure syndromes
A hallmark of cancer is the ability of cells to grow uncontrollably and indefinitely. This depends in part on a specialized enzyme complex called telomerase, which adds a unique DNA sequence (called telomere) to the ends of chromosomes to maintain genome integrity. We have recently identified various natural sequence changes in this enzyme complex in patients who suffer from bone-marrow failure syndromes. While bone marrow failure is the most common cause of death, pulmonary disease, immunodeficiency, and some of the most aggressive forms of cancer affecting the GI and blood (AML or CML) are also frequently observed in these patients. More recently, we have also discovered mutations in proteins that directly bind to telomeres and protect the chromosomes. We hypothesize that natural sequence changes in these proteins can cause genome instability, which may lead to the disease manifestation and cancer development. We, therefore, plan to characterize the disease-associated mutations for their effects on marrow failure and cancer development. These studies will offer new insights into the normal mechanisms of genome maintenance and hematopoiesis, and may lead to the development of novel therapeutic strategies against cancer.

- Basic biology of human Lassa hemorrhagic fever virus and the host immunological responses to viral infn
Approximately 15-20% of patients hospitalized for Lassa fever viral infection die from hemorrhages as a result of multisystemic failures. Due to the severe morbidity and high mortality rate, the lack of immunization and effective treatment modality, the ease of introduction to a susceptible human population and its ability to spread through human contacts, Lassa fever virus (LASV) has been classified by the Center for Disease Control and Prevention (CDC) as a Category A pathogen that can potentially be employed as a bio-weapon. Therefore, efforts to understand the basic biology of the virus in order to facilitate the development of effective antiviral strategies are of great importance to human health and to our national security. Such efforts, however, are hampered by the lack of a full-length infectious cDNA clone of the virus and the necessary containment restrictions for work with this virus in the laboratory. We have recently developed a simple, non-hazardous LASV minigenome system to examine the basic requirements of viral replication and virus-like particle formation. In addition, recent evidence suggest that viral infection often leads to a generalized suppression of adaptive immunity; the exact mechanism by which LASV modulates the host immune response has yet to be elucidated. We plan to determine the viral factor(s) that are responsible for this seemingly paradoxical immunological phenomenon. These efforts will offer new insights into understanding the basic biology of Lassa virus and its role in hemorrhagic pathogenesis, which may ultimately lead to the development of novel antiviral strategies and effective vaccine against a deadly form of hemorrhagic viral infections.

- Possible roles of the novel retrovirus XMRV and host factor(s) in human prostate cancer development
Ribonuclease L (RNase L) is activated in response to viral infection of mammalian cells. It degrades incoming viral RNA as well as cellular RNA in an effort to inhibit virus amplification. Genetic lesions of RNase L, therefore, impair this innate antiviral response and allow for the establishment of viral infection and replication. Indeed, a novel gamma-retrovirus (XMRV) has recently been reported in up to 40% of prostate cancer patients who carry a less functional variant allele of the RNase L gene. Replication of XMRV is sensitive to inhibition by INF-beta, which is a known strong activating signal of the innate-antiviral response pathway. The molecular clone of XMRV has been constructed, which has allowed for production of infectious viruses purely from XMRV-plasmid transfection into appropriate cells. Using this and other convenient systems currently available in our laboratory, we are interested in examining the possible role of XMRV infection in prostate cancer development. In addition, we are analyzing the role of the xpr1 protein as the receptor for XMRV as well as characterizing its other yet unknown function(s) in normal and malignant cells. These efforts will offer important and novel insights into the possible role of XMRV infection in prostate cancer development and of the Xpr1 protein in benign and cancerous conditions.

Honors / Awards:

Special Fellow of the Leukemia & Lymphoma Society of America (2003-2006),

Scholar of the American Cancer Society (2006-2010),

Established Researcher (Award) from the AA & MDS International Foundation, Inc. (2006-2008),

Graduated with Honors (B.S. & M.A. from UCLA), UCLA Presidential Undergraduate Research Fellowship, UCLA College Honors Undergraduate Fellowship, UCLA Chancellor's Leadership Award, UNC Chang Memorial Graduate Studentship Award,

Seed Funds awarded by the Emory Winship Cancer Institute (WCI-2004), the Emory University Research Council (URC-2005), the Emory Digestive Diseases R&D Center (DDRDC-2005), the Emory Center for AIDS Research (CFAR-2006), the Southeast Regional Center of Excellence for Emerging Infections and Biodefense (SERCEB-2007), Emory Pathology Dept (2003- ), and Emory Chemistry Dept (2008)

,

Emory's One-in-One-Hundred Mentor Award, 2008

Selected Publications:

Published and Accepted Research Articles -

Lan, S., L. M. Shelde, J. Wang, N. Kumar, H. Ly*, and Y. Liang*. 2009. Development of infectious clones for virulent and avirulent Pichinde viruses - a model virus to study arenavirus-induced hemorrhagic fevers. J. Virol. (in press) (*corresponding authors)

Liang, Y., S. Lan, and H. Ly. 2009. Molecular Determinants of Hemorrhagic Fever Arenavirus Infection. Annals NY Acad. Sci. (in press)

Ly, H. 2009. Genetic and Environmental Factors Influencing Human Diseases with Telomere Dysfunction. Int'l J Clin. & Exp. Medicine (invited review article) (in press).

Carroll, K. A. and H. Ly. 2009. Telomere Dysfunction in Human Disease: The Long and Short of It! Int'l J Clin. & Exp. Pathol. (invited review article) (in press).

Ly, H. 2008. Telomerase regulation in HTLV-I infection. Blood. 112(7):2603-4. (invited commentary article)

Junko, T*, Ly, H*, Yamaguchi, H., Carroll, K.A., Fumiko, K., Kazuhiro, S., Yoshio, M., Ayako, W., Seiji, G., Koiti, I. and Dan, K. 2008. Identification and Functional Characterization of Novel Telomerase Variant Alleles in Japanese Patients with Bone-Marrow Failure Syndromes. Blood Cell Mol. Dis. 40(2):185-191. (*equally contributed authors).

Lan, S., McLay, L., Aronson, J., Ly, H*., and Liang, Y*., 2008. Genome comparison of virulent and avirulent strains of the arenavirus Pichinde. Arch. Virol. 153:1241-50. (*corresponding authors).

Tang, F, Zhang, J.S., Liu W., Zhao Q.M., Zhang F., Wu X.M., Yang H., Ly H., Cao W.C. 2008. Failure of Japanese encephalitis vaccine and infection in inducing neutralizing antibodies against West Nile virus, People's Republic of China. Am J Trop Med Hyg. 78(6):999-1001.

Tang, F., Liu, W., Zhang, F., Xin, Z.T., Wei, M.T., Zhang, P.H., Yang, H., Ly, H., Cao, W.C. 2008. IL-12 RB1 Genetic Variants Contribute to Human Susceptibility to Severe Acute Respiratory Syndrome Infection among Chinese. PLoS ONE. 3(5):32183.

Kumar, N., Xin, Z.T., Liang, Y.H., Ly, H., and Liang, Y. 2008. NF-kB signaling differentially regulates influenza viral RNA synthesis. J. Virol. 82(20):9880-9.

Liang, Y, Huang, T, Ly, H, Parslow TG, Liang, Y. 2008. Mutational analyses of packaging signals in the influenza viral PA, PB1, and PB2 genomic RNA segments. J. Virol. 82(1):229-236.

Tomlinson, R.L., Abreu, E.B., Ziegler, T., Ly, H., Counter, C.M., Terns, R.M., Terns, M.P., 2008. Telomerase reverse transcriptase is required for the localization of telomerase RNA to Cajal bodies and to telomeres in human cancer cells. Mol. Biol Cell. 19(9):3793-800.

Xin, ZT, Beauchamp, AD, Calado, RT, Bradford, JW, Regal, JA, Shenoy, A, Liang, Y, Lansdorp, PM, Young, NS, Ly, H., 2007. Functional characterization of natural telomerase mutations found in patients with hematological disorders. Blood. 109(2):524-32.

Gipson, CL, Xin, ZT, Danzy, SC, Parslow, TG, and Ly, H. 2007. Functional Characterization of Yeast Telomerase RNA Dimerization. J. Biol. Chem. 282(26):18857-18863.

Danzy, S., Su, C. Y., Park, S., Li, S. Y., Ferraris, A. M., and Ly, H. 2006. Absence of pathogenic mutations in the telomerase RNA gene (hTERC) in patients with myeloproliferative disorders. Leukemia 20(5):893-894.

Savage, S. A., Calado, R. T., Xin, Z. T., Ly, H., Young, N. S., and Chanock, S. J. 2006. Genetic Variation in Telomeric Repeat Binding Factors 1 and 2 in Aplastic Anemia. Exp. Hematol. 34:664-671.

Ly, H*., Calado, T.R., Allard, P., Baerlocher, G.M., Lansdorp, P.M., Young, N.S., and Parslow, T.G. 2005. Functional characterization of telomerase RNA variants found in patients with hematological disorders. Blood. 105(6):2332-2339. (*corresponding author)

Khan, M.A., Kao, S, Eri, M., Hiroaki, T., Gaur,R., Opi, S., Gipson, C.L., Parslow, T.G., Ly, H., and Strebel, K. 2005. Viral RNA is required for the association of APOBEC3G with HIV-1 nucleoprotein complexes. J. Virol. 79(9):5870-5874.

Yamaguchi, H*., Calado, T.R*., Ly, H.*, Baerlocher, G.M., Chanock , S.J., Lansdorp, P.M., and Young, N.S. 2005. Mutations in TERT, the gene for human telomerase reverse transcriptase, in patients with aplastic anemia. New Engl. J. Med. 352(14):1413-1424. (*equally contributed authors)

Ly, H., Schertzer. M., Jastaniah, W., Davis, J., Yong, S. L., Ouyang, Q., Blackburn, E.H., Parslow, T.G., and Lansdorp, P.M. 2005. Mutations in both alleles of the telomerase RNA template gene (TERC) in a patient with Dyskeratosis Congenita. Blood 106(4):1246-1252.

Lin, J, Ly, H., Hussain, A., Abraham, M., Pearl, S., Tzfati, Y., Parslow, T.G., and Blackburn, E.H. 2004. A universal telomerase RNA core structure contains a conserved pseudoknot required for binding the telomerase catalytic protein. P.N.A.S. 101(41):14713-14718.

Anyanful, A., Ono, K., Johnsen, R.C., Ly, H, Jensen, V. Baillie, D.L., and Ono, S. 2004. The RNA-binding protein SUP-12 controls muscle-specific splicing of the ADF/cofilin premRNA in Caenorhabditis elegans. J. Cell Biol 167(4):639-647.

Ly, H., Blackburn, E.H., and Parslow, T.G. 2003. Comprehensive structure-function analysis of the core domain of the human telomerase RNA. Mol. Cell. Biol. 23(19):6849-6856.

Ly, H*., Xu, L*, Rivera, M., Parslow, T.G., and Blackburn, E.H. 2003. A role for a novel "trans-pseudoknot" RNA-RNA interaction in the functional dimerization of human telomerase. Genes & Dev. 17:1078-1083. (*equally contributed authors)

Ly, H. and Parslow, T.G. 2002. Bipartite signal for genomic RNA dimerization in Moloney murine leukemia virus. J. Virol . 76(7): 3135-3144.

Ly, H., Nierlich, D.P., Olsen, J.C. and Kaplan, A.H. 2000. Functional characterization of the dimer linkage structure RNA of Moloney murine sarcoma virus. J. Virol. 74(21): 9937-9945.

Ly, H., Nierlich, D.P., Olsen, J.C., and Kaplan, A.H. 1999. Moloney murine sarcoma virus genomic RNAs dimerize via a two-step process: A concentration-dependent kissing loop interaction is driven by contact between consecutive guanines. J. Virol. 73(9): 7255-7261.