1996 B. S. with Distinction in Microbiology, University of Hawaii at Manoa, Honolulu, Hawaii

Work Experience and Professional History

Military Training

1991 Basic Military Training and Non-Commissioned Officer Training, Singapore Armed Forces
1993 Platoon Sergeant, Singapore Armed Forces

Honors and Awards

1994 Dean’s List, College of Natural Sciences, University of Hawaii at Manoa, Honolulu, Hawaii
1994-1996 Asian Pacific Scholar, University of Hawaii at Manoa, Honolulu, Hawaii
1995- present National Golden Key Honour Society Member, University of Hawaii at Manoa, Honolulu, Hawaii
1996 Obstetrics and Gynecology Award, Biomedical Sciences Symposium, University of Hawaii at Manoa, Honolulu, Hawaii
2000 American Society for Microbiology, Hawaii Branch, Student Presentation Award, University of Hawaii at Manoa, Honolulu, Hawaii

Bibliography

1. Qin X, Garibay-Tupas J, Chua PK, Cachola L, Bryant-Greenwood GD. An autocrine/paracrine role of human decidual relaxin: Interstitial collagenase (MMP-1) and tissue plasminogen activator (tPA). Biology of Reproduction 1997;56:800-11.
   
2. Qin X, Chua PK, Ohira RH, Bryant-Greenwood GD. An autocrine/paracrine role of human decidual relaxin: Stromelysin-1 (MMP-3) and tissue inhibitor of matrix metalloproteinase (TIMP-1). Biology of Reproduction 1997;56:812-20.
   
3. Nerurkar VR, Chua PK, Hoffmann PR, Dashwood W-M, Shikuma CM, Yanagihara R. High prevalence of GB virus C/hepatitis G virus infection among homosexual men infected with human immunodeficiency virus type 1: Evidence for sexual transmission. Journal of Medical Virology 1998;56:123-7.
   
4. Nerurkar VR, Chua PK, Shikuma CM, Dashwood W-M, Milne CIP, Woodward CL, et al. Gradual loss of IgG antibodies against hepatitis G virus in a patient with AIDS. Hawaii Medical Journal 1998;57:733-4.
   
5. Nerurkar VR, Woodward CL, Nguyen HT, Miller FD, Tashima LT, Zalles-Ganley A, et al. Lack of association between TT virus infection and injection drug use or high-risk heterosexual activity in Vietnam. International Journal of Infectious Disease 1999;3:181-5.
   
6. Chua PK, Nerurkar VR, Yu Q, Woodward CL, Melish ME, Yanagihara R. No etiological association between Kawasaki syndrome and infection with parvovirus B19, human herpesvirus 8, TT virus, GB virus C/hepatitis G virus or Chlamydia pneumoniae. The Pediatric Infectious Disease Journal 2000;19:477-9.
   
7. Lin C-L, Kyono W, Tongson J, Chua PK, Easa D, Yanagihara R, et al. Fecal excretion of a novel human circovirus, TT virus, in healthy children. (Clinical and Diagnostic Laboratory Immunology: In press).
   
8. Chua PK, Yu Q, Nerurkar VR, Yamamoto KS, Melish ME, Yanagihara R. Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in the acute phase of Kawasaki syndrome. (Pediatric Research: In preparation).
   
9. Chua PK, Song J-W, Morita C, Masuzawa T, Kadosaka T, Yanagihara R. Pathogenic potential for arvicolid-rodent-borne hantaviruses. (Scandinavian Journal of Infectious Disease: In preparation).
   
10. Chua PK, Nerurkar VR, Ieong M-C, Dashwood W-M, Shikuma CM, Richmond-Crum SM,et al. Prevalence and genotypes of GB virus C/hepatitis G virus in HIV-1 infected individuals (Viral Hepatology: In preparation).
    
    

Published Abstracts

Qin X, Chua PK, Bryant-Greenwood G. Control of matrix metalloproteinase by human relaxins H2 in the fetal membrane. Gordon Research Conference, NH, July 1995

Chua PK, Qin X, Bryant-Greenwood G. Control of matrix metalloproteinase by human relaxins H1 and H2 in the human fetal membrane. Biomedical Sciences Symposium, University of Hawaii at Manoa, Honolulu, HI, April 20, 1996

Chua PK, Bryant-Greenwood G. Control of matrix metalloproteinase by human relaxins H1 and H2 in the human fetal membrane. 21st Annual West Coast Biological Sciences Undergraduate Research Conference, Point Loma Nazarene College, San Diego, CA, April 27, 1996

Chua PK, Bartram L, Nerurkar VR, Shikuma CM, Dashwood W-M, Yanagihara R. Hepatitis G virus infection among individuals infected with human immunodeficiency virus type 1: Evidence for sexual transmission. Biomedical Sciences Symposium, University of Hawaii at Manoa, Honolulu, HI, April 11, 1997

Chua PK, Nerurkar VR, Shikuma CM, Dashwood W-M, Hoffmann PR, Yanagihara R. Prevalence of and co-infection with hepatitis C and G viruses among HIV-1-infected individuals in Hawaii. 4th Asia-Pacific Congress of Medical Virology, Seoul, Korea, November 3-5, 1997

Chua PK, Ieong M-C, Nerurkar VR, Dashwood W-M, Shikuma CM, Richmond-Crum SM, et al. Parenteral and sexual transmission of hepatitis G virus (HGV) among HIV-1 infected individuals. Biomedical Science Symposium, University of Hawaii at Manoa, Honolulu, HI, April 11, 1998

Chua PK, Ieong M-C, Nerurkar VR, Dashwood W-M, Shikuma CM, Richmond-Crum SM, et al. Parenteral and sexual transmission of hepatitis G virus (HGV) among individuals infected with HIV-1. 17th Annual American Society For Virology Meeting, University of British Columbia, Canada, July 11-15, 1998

Woodward CL, Nguyen HT, Nerurkar VR, Tashima LT, Chua PK, Pham KC, et al. Prevalence of a recently described post-transfusion hepatitis-related DNA virus (TTV) among HIV-1-infected individuals in Vietnam: Evidence for non-parenteral transmission. 36th Annual Meeting Of The Infectious Diseases Society of America, Denver, Colorado, November 12-15, 1998

Chua PK, Nerurkar VR, Ieong M-C, Dashwood W-M, Hoffmann PR, Shikuma CM, et al. Prevalence and genotypes of hepatitis C virus among HIV-1-infected high-risk behavior groups in Hawaii. RCMI International AIDS Symposium, San Juan, Pueto Rico, November 15-18, 1998

Nerurkar VR, Chua PK, Ieong M-C, Dashwood W-M, Dashwood CM, Richmond-Crum SM, et al. Infection with GB virus C/hepatitis G virus (GBV-C/HGV), an orphan flavivirus, among HIV-1-infected individuals in Hawaii. RCMI International AIDS Symposium, San Juan, Pueto Rico, November 15-18, 1998

Nerurkar VR, Nguyen HT, Pham KC, Woodward CL, Miller FD, Chua PK, et al. Sexual transmission of GB virus C/hepatitis G virus among individuals at risk of human immunodeficiency virus type 1 and hepatitis C virus infection in Vietnam. RCMI International AIDS Symposium, San Juan, Pueto Rico, November 15-18, 1998

6th Internation Kawasaki Disease Symposium, Hilton Waikoloa Village, Waikoloa, Hawaii, February 11-14, 1999

Tongson JM, Woodward CL, Nerurkar VR, Nguyen HT, Miller FD, Tashima LT, et al. Lack of association between a recently described post transfusion hepatitis-related DNA virus, TT virus among individuals at-risk for hepatitis C virus and human immunodeficiency virus type 1 infection in Vietnam. Biomedical Sciences Symposium, University of Hawaii at Manoa, Honolulu, HI, April 9, 1999

Chua PK, Nerurkar VR, Yu Q, Woodward CL, Melish ME, Yanagihara R. Failure to demonstrate etiological association between recently described microbial pathogens and Kawasaki syndrome. Biomedical Sciences Symposium, University of Hawaii at Manoa, Honolulu, HI, April 9, 1999

Chua PK, Yu Q, Nerurkar VR, Yamamoto KS, Melish ME, Yanagihara R. Elevated matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in the acute phase of Kawasaki syndrome. Biomedical Sciences Symposium, University of Hawaii at Manoa, Honolulu, HI, April 9, 1999

Chua PK, Yu Q, Nerurkar VR, Yamamoto KS, Melish ME, Yanagihara R. Elevated matrix metalloproteinase 9 (MMP-9) activity in Kawasaki syndrome. 1999 Pediatric Academic Societies' Annual Meeting; San Francisco, CA, May 1-4, 1999 

Chua PK, Nerurkar VR, Ieong M-C, Dashwood W-M, Shikuma CM, Richmond-Crum SM, et al. Descriptive and molecular epidemiology of hepatitis C virus (HCV) and GB virus C/hepatitis G virus (GBV-C/HGV) among HIV-1-infected individuals in Hawaii. 6th International Symposium on Hepatitis C & Related Viruses, National Institutes of Health, Bethesda, Maryland, June 6-9, 1999

Nerurkar VR, Woodward CL, Nguyen HT, Miller FD, Tashima L, Zalles-Ganley A, et al. 6th International Symposium on Hepatitis C & Related Viruses, National Institutes of Health, Bethesda, Maryland, June 6-9 1999

Chua PK, Nerurkar VR, Woodward CL, Yu Q, Melish ME, Yanagihara R. Failure to demonstrate etiological association between Kawasaki syndrome and TT virus (TTV), human herpesvirus 8 (HHV 8), GB virus C/hepatitis G virus (GBV-C/HGV) and parvovirus B19 infection. 18th Annual American Society For Virology Meeting, University of Massachusetts, Amherst, July 10-14, 1999

Chua PK, Yanagihara R, Nerurkar VR. Modulation of adhesion molecule expression by tumor necrosis factor-a in endothelial cells: Possible pathogenic mechanism in Kawasaki syndrome. Biomedical Sciences Symposium, University of Hawaii at Manoa, Honolulu, HI, April 14, 2000

Chua PK, Nerurkar VR, Woodward CL, Yu Q, Melish ME, Yanagihara R. Failure to demonstrate etiological association between Kawasaki syndrome and TT virus (TTV), human herpesvirus 8 (HHV8), GB virus-C/hepatitis G virus (GBV-C/HGV) and parvovirus B19 infection. Annual Spring Meeting for the American Society for Microbiology, Hawaii Branch, University of Hawaii at Manoa, Honolulu, HI, April 15, 2000

Lin CL, Kyono W, Tongson J, Chua PK, Easa D, Yanagihara R, et al. Detection of a novel human circovirus, TT virus (TTV), in feces of healthy children. Annual Spring Meeting for the American Society for Microbiology, Hawaii Branch, University of Hawaii at Manoa, Honolulu, HI, April 15, 2000

Chua PK, Song J-W, Morita C, Yanagihara R. Pathogenicity of arvicolid-rodent-borne hantaviruses predicted by rodent mitochondrial DNA analysis. 19th Annual American Society For Virology Meeting, Colorado State University, Fort Collins, July 8-12, 2000

Lin CL, Kyono W, Tongson J, Chua PK, Easa D, Yanagihara R, et al. Detection of a novel human circovirus, TT virus (TTV), in feces of healthy children. 19th Annual American Society For Virology Meeting, Colorado State University, Fort Collins, July 8-12, 2000

 
 

1. Descriptive and molecular epidemiology of HIV-1-infected women in Hawaii

Background: The objective of this project is 1) to characterize HIV-1 infection among women in Hawaii in terms of demographic and risk factors, clinical manifestations, HIV-1 genotypes, and concurrent and complicating infections. In particular to characterize HIV-1 infection in this population in terms of host factors such as time of seroconversion, age, ethnicity, place of birth, high risk behaviours and presence of opportunistic infections, 2) to investigate the viral characteristics of HIV-1 in these individuals including HIV-1 subtypes, the intra- and inter-patient heterogeneity of viral strains, and viral evolution over time, 3) to analyze the associations between certain host, viral, and environmental factors, eg. the association between viral characteristics such as SI phenotype, antigenic variation, macrophage tropism, and glycosylation sites and host factors such as CD4+ level, opportunistic infections, high risk behaviour, and 4) to compare the genotypes of HIV-1 in PBMC and vaginal lavage.

Results: 9/31 (29%) HIV-1 infected women were seropositive for HCV and were also IDU. HCV was detected by PCR in plasma of 7/9 (78%) HCV antibody-positive women but in none of the HCV antibody-negative women. HPV 6b, 18, 61 and 66 DNA sequence were detected in cervical vaginal lavage specimens of 13 of 30 (43%) women. 4 of 31 (13%) women were commercial sex workers and all 4 were PCR positive for HPV gene sequences.

Significance: A strong association was demonstrated between HCV seropositivity and IDU (p<0.0001), and HPV gene sequences and multiple sex partners. The study shows that opportunistic infection of other viruses such as HPV and HCV can occur in HIV-1 infected women, depending on their high risk behaviour.

2. Molecular epidemiology of hantavirus in voles captured from Alaska, Japan, Taiwan and Korea and use of mtDNA to predict pathogenicity of arvicolid-rodent-borne hantaviruses

Background: Hantavirus belongs to the family Bunyaviridae, and is characterized by negative-sense tri-partite genome. Diseases associated with hantavirus infection includes hantavirus pulmonary syndrome, with a fatality of around 50%, hemorrhagic fever with renal syndrome (mortality 10%), and nephropatia epidemica (mortality 1%). The objective of this project was to try and determine if hantaviruses exist in Clethrionomys rufocanus, C. rutilus, Eothenomys regulus, E. smithii, E. andersoni, Micotus pennsylvanicus, M. montebelli as well as Suncus murinus. In addition, DNA was extracted from these voles for the amplification of mitochondrial DNA sequences.

Results: We were unable to detect hantavirus gene sequences or antibodies in any of the captured Eothenomys, S. murinus, M. pennslyvanicus or C. rutilus by reverse transcription-polymerase chain reaction or immunofluorescence, respectively. However, we were able to amplify hantavirus gene sequences in C. rufocanus captured from Japan. Genetic analysis of a short fragment from the S segment showed it was 98% similar to the hantavirus sequence published by Arikawa et al., which was also amplified from C. rufocanus. Moreover, using mtDNA as a molecular marker, we predict that both the Clethrionomys (Puumala and Puumala-like virus) and Eothenomys (Puumala-like and Muju virus) species are carriers of pathogenic hantaviruses, while hantaviruses harbored by the Microtus (Prospect Hill, Tula, Isla Vista virus) species do not seem to be pathogenic.

Significance: Although we were unable to amplify hantavirus in any of the captured voles, it is still possible that hantaviruses exists in these voles out in the wild. However, we do show that the use of mtDNA can be used in predicting the pathogenicity of arvicolid-borne hanatviruses.

 

Ph.D. Dissertation Topic

Background: Kawaski syndrome is an acute febrile illness affecting children of unknown etiology. Epidemiological and clinical evidence suggests Kawasaki syndrome is caused by an infectious agent. To determine if recently described orphan viruses could be the etiological cause of Kawasaki syndrome, we screened acute phase plasma/serum and peripheral blood mononuclear cells for the presence of microbial sequences.

Results: We were unable to amplify or detect TT virus, GB virus C/hepatitis G virus, human herpesvirus 8, Chlamydia pneumoniae or parvovirus B19 from plasma/serum, urine or PBMCs of 123 patients. Moreover, our serological data indicates that Kawasaki syndrome is not a result of parvovirus B19 infection.

Significance: Even though the data are largely negative, it does not rule out the possibility that Kawasaki syndrome has an infectious etiology. However, it is possible that the incriminating agent is as yet not detectable by classical molecular methods.

2. Possible use of matrix metalloproteinase as a diagnostic marker in Kawasaki syndrome

Background: Kawasaki syndrome is an acute febrile disease, mainly affecting children, with unknown etiology. Clinical manifestations include high fever, immunoregulatory abnormalities, vasculitis and coronary aneurysms. Matrix metalloproteinases (MMPs) are a class of enzymes capable of degrading extracellular matrices, and MMP-9 have been implicated in aortic aneurysm. In addition, MMP-9 is secreted complexed to its natural inhibitor, tissue inhibitor of metalloproteinase 1 (TIMP-1). Thus, the objective of this study was to ascertain if MMP-9 and/or TIMP-1 are up-regulated in Kawasaki syndrome, and possibly utilize MMP-9 and/or TIMP-1 as a diagnostic marker.

Results: In 27 paired-samples studied, there was a significant difference in the amount of MMP-9 enzymes and protein as well as TIMP-1 protein levels in the plasma between the acute and convalescent phase. In addition, MMP-9 and TIMP-1 protein levels were higher in the acute phase compared to febrile non-Kawasaki patients, non-febrile patients and healthy individuals.

Significance: From this study, we showed that MMP-9 enzyme and protein as well as TIMP-1 protein are significantly up-regulated in the plasma during the acute phase of Kawasaki syndrome compared to the convalescent phase, febrile patients without Kawasaki, non-febrile patients and healthy individuals. Thus, these biological molecules may be used a diagnostic marker in Kawasaki syndrome. Furthermore, the elevated MMP-9 levels may indicate a possible means by which coronary aneurysm could occur.

3. Cytokines do not regulate the production of matrix metalloproteinase 9 in endothelial cells

Background and Objective: Matrix metalloproteinase 9 (MMP-9) is an enzyme capable of degrading collagen type IV, gelatin and fibronectin. The presence of numerous transcription activator binding sites in the promoter region of the human MMP-9 gene indicates possible involement of various transcription factor that could regulate MMP-9 gene expression and subsequent protein production. Kawasaki syndrome is characterized by increases in various cytokine levels, including Interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha and interferon-gamma. To elucidate if any of the pro-inflammatory cytokines could be involved in increasing MMP-9 protein levels, we stimulated human umbilical vein endothelial cells with various cytokines known to be elevated in Kawasaki Syndrome.

Results: Using gelatin zymography, we were unable to detect MMP-9 enzyme from conditioned media of HUVEC cells treated with cytokines.

Conclusions: Elevated MMP-9 observed in KS was probably being produced by some other cellular source, such as smooth muscle cells, pericytes or immune cells.

Background and Objective: Adhesion molecules (ICAM-1 and E-selectin) are rarely expressed on the surfaces of endothelium, but are expressed when induced by pro-inflammatory cytokines. The presence of these adhesion molecules serves to act as anchorage for immune cells, and allow these cells to migrate out into the extracellular matrix. Monocyte chemoattractant protein forms a gradient that attracts inflammatory cells to sites of inflammation. We hypothesized that both TNF-a and VEGF, a cytokine capable of causing vascular permeability, which are elevated in the acute phase of Kawasaki Syndrome, have the ability to increase the expression levels of adhesion molecules and MCP-1 in endothelial cells.

Results: Using semi-quantitative RT-PCR, we found that physiological concentrations of TNF-a observed in KS induces ICAM-1 and E-selectin expression in a time and dose dependent manner, with the highest gene expression of both adhesion molecule occuring 3 h post-stimulation. In addition, MCP-1 gene levels were highest 6 h post-stimulation. VEGF did not significantly increase the expression levels of MCP-1 or E-selectin when compared to non-stimulated cells.

Significance: Elevated levels of TNF-a in KS may play a significant role in increasing adhesion molecule expression in the coronary endothelium. This increased levels of adhesion molecule, coupled with increased MCP-1 may indicate an inflammatory response to an infectious agent. Moreover, it implies that the immune cells, which are capable of producing MMP-9, are attracted to these sites and may migrate out into the extracellulare matrix where it can cause vascular remodeling. Further studies using coronary artery endothelial cells are underway