Dr. Chen is a Research Faculty member in Dr. Kreiswirths’ laboratory and studies the molecular epidemiology of antimicrobial resistance and infectious disease, with particular focus on carbapenem-resistant Enterobacteriaceae (CRE), Methicillin-resistant Staphylococcus aureus (MRSA), and multiresistant mycobacteria.
Currently, Dr. Chen is seeking to decipher the molecular evolution of the emergence of CRE. CRE have been described as “nightmare bacteria”, and been classified as an “urgent threat” by CDC. CRE have increased over the past decade and grown resistance to even the most powerful antibiotics. The worldwide dissemination of CRE is predominately associated with a single K. pneumoniae clone, ST258. Using the whole genomic analysis, Dr. Chen and his colleagues have revealed that the ST258 is a hybrid strain that originated as a large chromosomal recombination. Meanwhile, this superclone is under significantly diversification, primarily due to the recombination of antigen encoded capsular polysaccharide synthesis (cps) region and plasmid acquisition. Thus far, they have sequenced over 300 CRE isolates, including the first two completely closed ST258 genomes; and have completely characterized over 50 carbapenem-resistant plasmids.
A major concern about CRE is that resistance targets are primarily carried on plasmids that can easily transfer the resistance to other bacteria. Another aspect of Dr. Chen’s work is to develop robust molecular detection platforms to track the dissemination of the life threatening bacteria, and more importantly, to explore CRE transmission from the traditional “strain epidemiology” to “plasmid epidemiology”. Using WGS technique and comparative genomic analysis, Dr. Chen has identified and characterized the epidemic drug-resistant plasmids prevailing in the epicenter of this epidemic (NY/NJ) and developed robust molecular tools to rapidly track the spread of these resistance plasmids.
In addition, he is currently leading several genomic projects at PHRI TB center, including the complete closure and genomic characterization of multi-drug resistant Mycobacterium tuberculosis, Klebsiella pneumoniae and S. aureus, using the combination of next generation Illumina sequencing and the third generation single-molecule real-time sequencing, and the RNAseq transcriptome analysis. His group use genomic sequencing together with informatics tools and clinical epidemiology to tackle the menace of emerging bacterial resistance.
Al Laham N, Chavda KD, Cienfuegos-Gallet AV, Kreiswirth BN, Chen L (2017) Genomic Characterization of VIM Metallo-beta-Lactamase-Producing Alcaligenes faecalis from Gaza, Palestine. Antimicrob Agents Chemother 61. PMI: 28848020
Bulman ZP, Chen L, Walsh TJ, Satlin MJ, Qian Y, Bulitta JB, Peloquin CA, Holden PN, Nation RL, Li J, Kreiswirth BN, Tsuji BT (2017) Polymyxin Combinations Combat Escherichia coli Harboring mcr-1 and blaNDM-5: Preparation for a Postantibiotic Era. MBio 8. PMI: 28743810
Chavda KD, Chen L, Fouts DE, Sutton G, Brinkac L, Jenkins SG, Bonomo RA, Adams MD, Kreiswirth BN (2016) Comprehensive Genome Analysis of Carbapenemase-Producing Enterobacter spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms. MBio 7. PMI: 27965456
Chen L, Chavda KD, Mediavilla JR, Zhao Y, Fraimow HS, Jenkins SG, Levi MH, Hong T, Rojtman AD, Ginocchio CC, Bonomo RA, Kreiswirth BN (2012) Multiplex real-time PCR for detection of an epidemic KPC-producing Klebsiella pneumoniae ST258 clone. Antimicrob Agents Chemother 56: 3444-3447. PMI: 22450983
Chen L, Chavda KD, Melano RG, Hong T, Rojtman AD, Jacobs MR, Bonomo RA, Kreiswirth BN (2014) Molecular survey of the dissemination of two blaKPC-harboring IncFIA plasmids in New Jersey and New York hospitals. Antimicrob Agents Chemother 58: 2289-2294. PMI: 24492370
Chen L, Chavda KD, Melano RG, Jacobs MR, Koll B, Hong T, Rojtman AD, Levi MH, Bonomo RA, Kreiswirth BN (2014) Comparative genomic analysis of KPC-encoding pKpQIL-like plasmids and their distribution in New Jersey and New York Hospitals. Antimicrob Agents Chemother 58: 2871-2877. PMI: 24614371
Chen L, Mathema B, Pitout JD, DeLeo FR, Kreiswirth BN (2014) Epidemic Klebsiella pneumoniae ST258 is a hybrid strain. MBio 5: e01355-01314. PMI: 24961694
Deleo FR, Chen L, Porcella SF, Martens CA, Kobayashi SD, Porter AR, Chavda KD, Jacobs MR, Mathema B, Olsen RJ, Bonomo RA, Musser JM, Kreiswirth BN (2014) Molecular dissection of the evolution of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae. Proc Natl Acad Sci U S A 111: 4988-4993. PMI: 24639510
DeLeo FR, Kennedy AD, Chen L, Bubeck Wardenburg J, Kobayashi SD, Mathema B, Braughton KR, Whitney AR, Villaruz AE, Martens CA, Porcella SF, McGavin MJ, Otto M, Musser JM, Kreiswirth BN (2011) Molecular differentiation of historic phage-type 80/81 and contemporary epidemic Staphylococcus aureus. Proc Natl Acad Sci U S A 108: 18091-18096. PMI: 22025717
Du H, Chen L, Tang YW, Kreiswirth BN (2016) Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae. Lancet Infect Dis 16: 287-288. PMI: 26842776
Eilertson B, Chen L, Chavda KD, Kreiswirth BN (2017) Genomic Characterization of Two KPC-Producing Klebsiella Isolates Collected in 1997 in New York City. Antimicrob Agents Chemother 61. PMI: 28167551
Kennedy AD, Otto M, Braughton KR, Whitney AR, Chen L, Mathema B, Mediavilla JR, Byrne KA, Parkins LD, Tenover FC, Kreiswirth BN, Musser JM, DeLeo FR (2008) Epidemic community-associated methicillin-resistant Staphylococcus aureus: recent clonal expansion and diversification. Proc Natl Acad Sci U S A 105: 1327-1332. PMI: 18216255
Kobayashi SD, Porter AR, Dorward DW, Brinkworth AJ, Chen L, Kreiswirth BN, DeLeo FR (2016) Phagocytosis and Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils. J Infect Dis 213: 1615-1622. PMI: 26768252
Li L, Cheung A, Bayer AS, Chen L, Abdelhady W, Kreiswirth BN, Yeaman MR, Xiong YQ (2016) The Global Regulon sarA Regulates beta-Lactam Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus In Vitro and in Endovascular Infections. J Infect Dis 214: 1421-1429. PMI: 27543672
Lynch T, Chen L, Peirano G, Gregson DB, Church DL, Conly J, Kreiswirth BN, Pitout JD (2016) Molecular Evolution of a Klebsiella pneumoniae ST278 Isolate Harboring blaNDM-7 and Involved in Nosocomial Transmission. J Infect Dis 214: 798-806. PMI: 27284091
MacVane SH, Pandey R, Steed LL, Kreiswirth BN, Chen L (2017) Emergence of Ceftolozane-Tazobactam-Resistant Pseudomonas aeruginosa during Treatment Is Mediated by a Single AmpC Structural Mutation. Antimicrob Agents Chemother 61. PMI: 28947473
Mediavilla JR, Patrawalla A, Chen L, Chavda KD, Mathema B, Vinnard C, Dever LL, Kreiswirth BN (2016) Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and blaNDM-5, Causing a Complicated Urinary Tract Infection in a Patient from the United States. MBio 7. PMI: 27578755
Shields RK, Chen L, Cheng S, Chavda KD, Press EG, Snyder A, Pandey R, Doi Y, Kreiswirth BN, Nguyen MH, Clancy CJ (2017) Emergence of Ceftazidime-Avibactam Resistance Due to Plasmid-Borne blaKPC-3 Mutations during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections. Antimicrob Agents Chemother 61. PMI: 28031201
Simpson G, Zimmerman R, Shashkina E, Chen L, Richard M, Bradford CM, Dragoo GA, Saiers RL, Peloquin CA, Daley CL, Planet P, Narachenia A, Mathema B, Kreiswirth BN (2017) Mycobacterium tuberculosis Infection among Asian Elephants in Captivity. Emerg Infect Dis 23: 513-516. PMI: 28221115
Yu F, Wang S, Lv J, Qi X, Guo Y, Tang YW, Kreiswirth BN, Wang L, Chen L (2017) Coexistence of OXA-48-Producing Klebsiella pneumoniae and Escherichia coli in a Hospitalized Patient Who Returned from Europe to China. Antimicrob Agents Chemother 61. PMI: 28115343