295H Animal Science/ Veterinary Medicine
1988 Fitch Avenue
University of Minnesota
St. Paul, MN 55108
B.S. and M.A., University of California, Los Angeles (UCLA)
Ph.D., University of North Carolina, Chapel Hill (UNC)
Post-doctoral, University of California, San Francisco (UCSF)
Molecular mechanisms of Lassa fever virus replication and host immune suppression: Lassa fever virus infection can lead to severe and sometime lethal hemorrhagic fever diseases in humans, for which there is no vaccine or effective drug. Studies of Lassa (LASV) and other pathogenic arenaviruses have been hindered by the strict requirement for BSL-4 containment to work with these select agents. We have recently developed an infectious molecular clone for a prototypic BSL2 arenavirus (i.e., Pichinde virus - PICV) as well as a safe and convenient mini-replicon system for LASV. We have also developed a safe and useful small animal model for Lassa fever by infecting guinea pigs with PICV. These novel systems have afforded us with unique resources and unprecedented opportunities to investigate in details the processes of viral genome replication/transcription and virulence. We are also interested in characterizing a novel functional mechanism of the Lassa viral nucleoprotein in mediating host innate immune suppression (Qi, et al., 2010, Nature, 468: 779-783). These efforts may lead the development of effective therapeutics against this deadly viral pathogen that can claim up to 5,000 deaths annually in the endemic areas of West Africa and is a constant bio-threat to our national security.
Roles of telomere-telomerase biology in human blood disorders and cancers: Patients with a serious form of blood disorder known as acquired aplastic anemia (AA) have very low blood counts due to marrow failure syndromes. We have recently shown that naturally occurring mutations in the telomere maintenance genes can predispose some of the patients to the development of AA (Yamaguchi, et al., 2005, New Engl J of Med; 2010, British J Haematol). The exact mechanisms of how these germ-line mutations lead to limited marrow stem-cell reserve and renewal capacity have not been characterized in details. We aim to investigate the molecular mechanisms by which telomere dysfunction can lead to ineffective hematopoiesis and increased cancer risk in patients with bone-marrow failure syndromes.
(For a comprehensive list of Dr. Ly's recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Yamaguchi, H.*, Calado, RT.*, Ly, H.*, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med. 2005 Apr 7;352(14):1413-24. (*co-first authors)
Lan, S., McLay, Schelde, L., Wang, J., Kumar N., Ly, H.*, Liang, Y*. Development of infectious clones for virulent and avirulent pichinde viruses: a model virus to study arenavirus-induced hemorrhagic fevers. J Virol. 2009 Jul;83(13):6357-62. (*corresponding authors)
Liang Y., Lan S., Ly, H. Molecular determinants of Pichinde virus infection of guinea pigs--a small animal model system for arenaviral hemorrhagic fevers. Ann N Y Acad Sci. 2009 Sep;1171 Suppl 1:E65-74.
Qi, X., Lan, S., Wang, W., Schelde, L.M., Dong, H., Wallet, G.D., Ly, H.*, Liang, Y.*, and Dong, C. Cap binding and immune evasion revealed by Lassa nucleoprotein structure. Nature. 2010. 468: 779-783. (*corresponding authors)
Ly, H. Telomere dynamics in induced pluripotent stem cells: Potentials for human disease modeling. World J Stem Cells. 2011 Oct 26;3(10):89-95.
Xin ZT, Ly, H. Characterization of interactions between naturally mutated forms of the TIN2 protein and its known protein partners of the shelterin complex. Clin Genet. 2011 Dec 30 [Epub ahead of print].
"Novel mechanism of immune evasion by arenaviral nucleoproteins", NIH/NIAID, R01 AI093580-01, 2012-2017, Ly (PI)
"Cap snatching mechanism of arenaviruses", NIH/NIAID, R56 AI091805-01, 2011-2013, Ly (PI)
Honors and Awards
2006-2011 American Cancer Society Scholar Award
2006-2008 Established Researcher Award, AA&MDS Int’l Foundation
2008 Inaugural One-in-One-Hundred Mentor Award (Emory University)
2003-2006 Leukemia & Lymphoma Society of America Special Fellowship