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致病性黴菌之流行病學及致病機轉

Epidemiology and Pathogenesis in Medical Mycology

致病性黴菌之流行病學及致病機轉

 


 

 

 

   

羅秀容 HSIU-JUNG LO

副研究員Associate Investigator
Phone: (037) 246-166 ext. 35516, 
Fax: (037) 586-457 
E-mail: hjlo@nhri.org.tw
 

 

 

 

After graduating from National Chung-Hsing University in Taiwan in 1987, Hsiu-Jung Lo was chosen for further graduate training in United States via Molecular, Cellular, and Developmental Biology program. She received her Ph.D. degree from Indiana University in Indiana in 1995 and worked as a Postdoctoral Fellow at Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA, before joining the Division of Clinical Research at National Health Research Institutes in 1999.
In the past decade, yeast infections have played an important role in nosocomial infections. Candida albicans is the most frequently isolated fungal pathogen in humans and has caused morbidity in immunocompromised hosts. Many currently available antifungal drugs have several problems including cytotoxicity side effects, being ineffective against some fungi, and leading to the development of resistance. The increasing prevalence of yeast infections highlights the need for better understanding the distribution and susceptibility of clinical yeast isolates in Taiwan and the mechanism of pathogenesis of yeast pathogens. Hence, the knowledge gained from these studies may be helpful for designing new effective antifungal agents and prolonging the effectiveness of existing drugs.

 

 

 

Research Interests

 

Dr. Lo main research interest is the epidemiology and pathogenesis of fungal infections.  She has used laboratory and epidemiological methods to determine prevalence of human fungal infections and to examine evolving issues related to resistance to antifungal agents in Taiwan.  She has also applied molecular tools to study the pathogenesis of fungal infections, specifically concerning factors modulating fungal virulence and mechanisms of drug resistance in Candida albicans – the most common and important human fungal pathogen.  The goals of her researches are to provide useful information for control and management of fungal infections in Taiwan and for developing novel antifungal agents with potential clinical application.

 

 

 

 

 

 

Epidemiology

Upon Dr. Lo’s return to Taiwan and joining the NHRI, she conferred with a group of mycologists and organized the “Taiwan Mycology Group”.  The purpose of this group was to establish a collaborative research environment and to identify problems and assist in resolving difficult issues related to management of fungal infections in Taiwan.  In a collaborative effort with the “Taiwan Surveillance of Antimicrobial Resistance” group, they have conducted three rounds of nationwide fungal surveillance study to determine prevalent types of fungal infections and the trends of drug susceptibilities of those isolates.  In addition, they also applied molecular typing to determine genetic relatedness of the clinical isolates, especially those exhibiting drug resistance.  In Taiwan, they found an association between fluconazole susceptibility and genetic relatedness among Candida tropicalis but not C. albicans isolates.  Among HIV-infected patients, they also determined that antibiotic treatment and lower CD4+ count (< 200 cells/mm3) were risk factors for oropharyngeal candidiasis and that antiretroviral therapy protected patients from developing candidiasis.  Furthermore, they found that when candidemia occurred in cancer patients undergoing chemotherapy, they were more likely to be infected by non-albicans Candida species that were less susceptible to fluconazole.  Dr. Lo’s team will continuously conduct TSARY and surveys on high-risk populations for fungal infections.

 Pathogeneisis

Dr. Lo initially observed that the non-filamentous cph1/cph1 efg1/efg1 C. albicans mutant was not lethal in a mouse model.  This model has provided her with a new insight for her ongoing study of pathogenesis and drug resistance in C. albicans infection.  Recently, Dr. Lo’s team have identified a key transcription factor, CaNdt80p, as a novel regulator of the gene CDR1, which is known to encode an efflux pump and is involved in drug resistance.  Furthermore, they found that CaNdt80p is involved directly or indirectly in drug resistance, nitric oxide inactivation, morphological switch, and enhancing the fungal cells’ survival and infectivity.  These findings suggest that CaNdt80p offers a new mechanism affecting the pathogenesis of C. albicans infection and provides an opportunity to develop potential antifungal therapeutics.  Currently, Dr. Lo’s team are using genome-wide approach to investigate the functions of CaNdt80p by identifying the targets of CaNdt80p.  In addition, they would also like to elucidate the mechanism for how a key factor, CaNdt80p, coordinates different networks in fungal pathogens.

 

 

 

 

 

Selected Publications (* corresponding author) 

 

1.Yang,Y.L., Wang,C.W., Chen, C.T. Wang, M.H., Hsiao, C.F., and Lo,H.J.* (2009). Non-lethal Candida albicans cph1/cph1 efg1/efg1 mutant partially protect mice from systemic infections by lethal wild-type cells. Mycological Research. 113, 388-390.

 

 

 

 

 

2.Wang,J.S., Yang,Y.L., Wu,C.J., Ouyang,K.J., Tseng,K.Y., Chen,C.G., Wang,H., and Lo,H.J. (2006). The DNA-binding domain of CaNdt80p is required to activate CDR1 involved in drug resistance in Candida albicans. J Med. Microbiol. 55, 1403-1411.

 

 

 

 

3.Chen,C.G., Yang,Y.L., Cheng,H.H., Su,C.L., Huang,S.F., Chen,C.T., Liu,Y.T., Su,I.J., and Lo,H.J.* (2006). Non-lethal Candida albicans cph1/cph1 efg1/efg1 transcription factor mutant establishing restricted zone of infection in a mouse model of systemic infection. Int J Immunopathol Pharmacol. 19, 561-565

 

 

 

 

4.Yang,Y.L., Lin,Y.H., Tsao,M.Y., Chen,C.G., Shih,H.I., Fan,J.C., Wang,J.S., and Lo,H.J.* (2006). Serum repressing efflux pump CDR1 in Candida albicans. BMC. Mol. Biol. 7, 22.

 

 

 

 

 

 

5.Lo,H.J., Wang,J.S., Lin,C.Y., Chen,C.G., Hsiao,T.Y., Hsu,C.T., Su,C.L., Fann,M.J., Ching,Y.T., and Yang,Y.L. (2005). Efg1 involved in drug resistance by regulating the expression of ERG3 in Candida albicans. Antimicrob. Agents Chemother. 49, 1213-1215.

 

 

 

 

 

 

6.Yang,Y.L., Li,S.Y., Cheng,H.H., and Lo,H.J.* (2005). Susceptibilities to amphotericin B and fluconazole of Candida species in TSARY 2002. Diagn Microbiol Infect Dis. 51, 179-183.

 

 

 

 

 

 

7.Hung,C.C., Yang,Y.L., Lauderdale,T.L., McDonald,L.C., Hsiao,C.F., Cheng,H.H., Ho,Y.A., and Lo,H.J.* (2005). Colonization of human immunodeficiency virus-infected outpatients in Taiwan with Candida species. J Clin Microbiol. 43, 1600-1603.

 

 

 

 

 

8.Chen,C.G., Yang,Y.L., Shih,H.I., Su,C.L., and Lo,H.J.* (2004). CaNdt80 is involved in drug resistance in Candida albicans by regulating CDR1. Antimicrob. Agents Chemother. 48, 4505-4512.

 

 

 

 

 


 

 

 

 

 

 

 

 

 

 


 

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