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Welcome to the Laboratory of Andrew Y. Koh, M.D. in the Departments of Pediatrics (Hematology/Oncology and Infectious Diseases) and Microbiology at the University of Texas Southwestern Medical Center.

We are broadly interested in understanding how resident intestinal microorganisms (particularly bacteria and fungi and collectively referred to as the gut microbiome) influence the health of human cancer and stem cell transplant patients: development of gut-derived microbial infections, graft-versus-host disease, and modulating host immune-mediated anti-tumor activity.

Our projects generally involve a mix of experimental approaches, ranging from in vitro model systems, to animal models, to advanced molecular biology techniques, next-generation sequencing approaches, and translational work with human patients. Please explore our website to find out more about the lab’s ongoing research and the people doing the work.

Andrew Y. Koh, M.D.
Assistant Professor
Andrew.koh@utsouthwestern.edu
214-648-3896

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Research

Candida albicans Gastrointestinal Colonization and Dissemination

Candida albicans, the most common human fungal pathogen, colonizes up to 80% of humans and is now the 4th leading cause of hospital-acquired infections. Surgical patients, premature babies, and cancer patients are particularly prone to developing invasive Candida infections.

We are particularly interested in how commensal anaerobic gut microbiota maintain C. albicans colonization resistance in the mammalian gut. We have shown that specific commensal anaerobic bacteria are critical for inducing gastrointestinal epithelial cells to produce gut immune effectors (such as hypoxia- inducible factor-1α, HIF-1α, and the antimicrobial peptide LL-37/CRAMP) that are essential for maintaining C. albicans colonization resistance. When commensal bacterial populations are disrupted via antibiotic therapy, gut immune effectors are markedly diminished, and Candida populations can overgrow and subsequently cause invasive disease.

We are now in the process of further elucidating both the direct bacterial-fungal and bacterial-host mechanisms that prevent C. albicans from colonizing the mammalian GI tract. By gaining insight into these mechanisms, we hope to apply these findings to human patients with hopes of preventing invasive C. albicans infections.

Role of the gut microbiota in modulating graft-versus-host-disease

Between 20-50% of patients undergoing allogeneic stem cell transplantation (SCT) develop graft-versus-host-disease (GVHD), a complex immune-mediated process in which the transplanted immune system (graft) attacks the organs of the recipient (host), resulting in 20% to 50% of HSCT patients.

Commensal gut bacteria have long been implicated in initiating and perpetuating GVHD. Our group and others have shown that specific commensal anaerobic bacteria are associated with protection from GVHD. Using metagenomic shotgun sequencing analysis, we were able to identify specific commensal bacterial species, what we term anti-inflammatory Clostridia (AIC), that were significantly depleted in pediatric GVHD patients. We then used a preclinical GVHD model to verify our clinical observations. Specific antibiotics that deplete AIC exacerbate GVHD in mice, whereas oral AIC supplementation increases gut AIC levels and mitigates GVHD in mice. Together, these data suggest that an antibiotic-induced AIC depletion in the gut microbiota is associated with the development of GVHD in pediatric SCT patients.

We are now in the process of further elucidating the mechanisms by which AIC modulate GVHD. By gaining insight into these mechanisms, we hope to apply these findings to human patients with hopes of preventing GVHD in patients.

Role of the gut microbiota in modulating host anti-tumor response

One of the major functions of the gut microbiome is the activation and education of host immune responses[7, 8]. Interestingly, in preclinical mouse models, the composition of the host gut microbiota is a major factor determining response to cancer therapy, both cytotoxic chemotherapy and immune checkpoint inhibitory therapy (ICT). In fact, germ-free or antibiotic treated tumor bearing mice do not respond to cancer therapy. But introducing specific gut microbiota in the murine GI tract results in improved cancer therapy response.

We recently completed a pilot study in adult melanoma patients receiving immune checkpoint inhibitor therapy (ICT). We performed gut microbiome and gut metabolome profiling on pre-therapy fecal samples. We identified unique gut microbiota and gut metabolites that were significantly enriched in ICT responders versus those who developed progressive disease.

We are now in the process of further elucidating the potential mechanisms by which these specific gut microbiota and metabolites may augment host response to cancer therapy by using in vitro functional immune assays and a preclinical melanoma model. By gaining insight into these mechanisms, we hope to apply these findings to cancer patients with hopes of optimizing response to cancer therapy.

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People

Dr. Andrew Y. Koh, MD
Principal Investigator

Laura Coughlin

Lab Manager

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Publications

Featured publications:

  • Koh AY, Köhler JR, Coggshall KT, Van Rooijen N, Pier GB. Mucosal damage and neutropenia are required for Candida albicans dissemination. PLoS Pathogens 2008; 4(2):e35 PMID:18282097. Abstract and Full Text

  • Fan D, Coughlin LA, Neubauer MM, Kim J, Kim M, Zhan X, Simms-Waldrip TR, Xie Y, Hooper LV, Koh AY. Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization. Nature Medicine 2015 Jul; 21(7):808-14. PMID:26053625. Abstract and Full Text

  • Lopez-Medina E, Fan D, Coughlin LA, Ho EX, Lamont IL, Reimmann C, Hooper LV, Koh AY. Candida albicans inhibits Pseudomonas aeruginosa Virulence through Suppression of Pyochelin and Pyoverdine Biosynthesis. PLoS Pathogens 2015 Aug 27; 11(8):e1005129. PMID: 26313907. Abstract and Full Text

  • Simms-Waldrip TR, Sunkersett G, Coughlin LA, Savani M, Arana C, Kim J, Kim M, Zhan X, Greenberg DE, Xie Y, Davies SM, Koh AY. Antibiotic-induced depletion of anti-inflammatory Clostridia is associated with the development of GVHD in pediatric stem cell transplant patients. Biology of Blood and Marrow Transplantation. 2017 May; 23(5):820-829: PMID: 28192251. Abstract and Full Text

Koh Lab publications:

  • Koh AY. Potential for Monitoring Gut Microbiota for Diagnosing Infections and Graft-versus-Host Disease in Cancer and Stem Cell Transplant Patients. Clinical Chemistry. 2017 Jul 18.  Abstract and Full Text

  • Koh AY.  The microbiome in hematopoietic stem cell transplant recipients and cancer patients: Opportunities for clinical advances that reduce infection. PLoS Pathogens 2017 Jun 29; 13(6):e1006342. PMID: 28662165.   There is no Abstract link.  Full Text

  • Simms-Waldrip TR, Sunkersett G, Coughlin LA, Savani M, Arana C, Kim J, Kim M, Zhan X, Greenberg DE, Xie Y, Davies SM, Koh AY. Antibiotic-induced depletion of anti-inflammatory Clostridia is associated with the development of GVHD in pediatric stem cell transplant patients. Biology of Blood and Marrow Transplantation. 2017 May; 23(5):820-829: PMID: 28192251. Abstract and Full Text

  • Kim J, Kim M, Koh AY, Xie Y, Zhan X. FMAP: Functional Mapping and Analysis Pipeline for metagenomics and metatranscriptomics studies. BMC Bioinformatics. 2016 Oct10; 17(1):420. PMID:27724866. Abstract and Full Text

  • Koh AY. Identifying host immune effectors critical for protection against Candida albicans infections. Virulence 2016 Oct 2; 7(7):745-7. PMID: 27336198. Abstract and Full Text

  • Piper HG, Fan D, Coughlin LA, Ho EX, McDaniel MM, Channabasappa N, Kim J, Kim M, Zhan X, Xie Y, Koh AY. Severe gut microbiota dysbiosis is associated with poor growth in patients with short bowel syndrome. J Parenter Enteral Nutr. 2016 Jul 12. PMID:27406942. Abstract and Full Text

  • Lopez-Medina E, Koh AY. The complexities of bacterial-fungal interactions in the mammalian gastrointestinal tract. Microbial Cell. 2016 Mar 16; 3(5):191-195. PMID:28357354. Abstract and Full Text

  • Lopez-Medina E, Fan D, Coughlin LA, Ho EX, Lamont IL, Reimmann C, Hooper LV, Koh AY. Candida albicans inhibits Pseudomonas aeruginosa Virulence through Suppression of Pyochelin and Pyoverdine Biosynthesis. PLoS Pathogens 2015 Aug 27; 11(8):e1005129. PMID: 26313907. Abstract and Full Text

  • Fan D, Coughlin LA, Neubauer MM, Kim J, Kim M, Zhan X, Simms-Waldrip TR, Xie Y, Hooper LV, Koh AY. Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization. Nature Medicine 2015 Jul; 21(7):808-14. PMID:26053625. Abstract and Full Text

  • Koh AY. Murine models of Candida gastrointestinal colonization and dissemination. Eukaryot Cell. 2013 Nov;12(11):1416-22. PMID: 24036344. Abstract and Full Text

Publications from AYK postdoctoral work, Harvard Medical School (2002-2008)

  • Koh AY, Mikkelsen PJ, Smith RS, Coggshall KT, Kamei A, Givskov M, Lory S, Pier GB. Utility of in vivo transcription profiling for identifying Pseudomonas aeruginosa genes needed for gastrointestinal colonization and dissemination. PLoS ONE, 2010 Dec 10; 5(12): e15131. PMID: 21170272. Abstract and Text

  • Kamei A*, Koh AY*, Gadjeva M, Priebe GP, Lory S, Pier GB. Analysis of Acquisition of Pseudomonas aeruginosa Gastrointestinal Mucosal Colonization and Horizontal Transmission in a Murine Model. Journal of Infectious Diseases. 2010 Jan; 201(1):71-80. PMID: 19938976 * Both authors contributed equally to this work. Abstract and Full Text

  • Koh AY, Priebe GP, Ray C, Van Rooijen N, Pier GB. Inescapable need for Neutrophils as Mediators of Cellular Innate Immunity to Acute Pseudomonas aeruginosa Pneumonia. Infection and Immunity.   2009 Dec; 77(12):5300-5310. PMID: 19805527. Abstract and Full Text

  • van Gennip M, Christensen LD, Alhede M, Phipps R, Jensen PO, Christophersen L, Pamp SJ, Moser C, Mikkelsen PJ, Koh AY, Tolker-Nielsen T, Pier GB, Hoiby N, Givskov M, Bjarnsholt T. Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes. Acta Pathologica, Microbiologica et Immunologica Scandinavica 2009 Jul; 117:537-46. PMID:19594494. Abstract and Full Text

  • Koh AY, Köhler JR, Coggshall KT, Van Rooijen N, Pier GB. Mucosal damage and neutropenia are required for Candida albicans dissemination. PLoS Pathogens 2008; 4(2):e35 PMID:18282097. Abstract and Full Text

  • Koh AY, Priebe GP, Pier GB. Virulence of Pseudomonas aeruginosa in a murine model of gastrointestinal colonization and dissemination in neutropenia.  Infection and Immunity 2005 Apr ; 73(4):2262-2272. PMID: 15784570. Abstract and Full Text

Publications from AYK residency, Harvard Medical School (1996-2002)

  • Koh AY, Pizzo PA. Empirical Oral Antibiotic Therapy for Low Risk Febrile Cancer Patients with Neutropenia.  Cancer Investigation  2002; 20(3): 420-433. PMID: 12025236. Abstract

  • Koh AY, Bernstein H.  Neonatal jaundice, animal-induced injuries, and immunizations.  Curr Opn Pediatr 2000; 12:413-425. PMID: 10943826. Abstract

  • Pizzo C, Mansbach J, Koh A, Tunnessen WW.  Pediatric Puzzler: new seizures in a 6-year old: expanding horizons.  Contemporary Pediatrics 1999; 16(8):25-33.

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Contact

Andrew Y. Koh, M.D.
Assistant Professor of Pediatrics and Microbiology
Director of Pediatric Hematopoietic Stem Cell Transplantation

University of Texas – Southwestern Medical Center
5323 Harry Hines Blvd.
Room H3.104
Dallas, TX 75390-9063

Email Andrew Koh

Administrative Contact:

Jacqui Harris

Email Jacqui Harris

Phone: 214-648-8594
Fax: 214-648-2764

UTSW Main Campus

UTSW Main Campus

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