Associate Professor, Department of Pediatrics (Infectious Diseases)
Assistant Professor, Department of Microbiology & Immunology
The medical community has long recognized fungi as important allergens for patients with asthma. Interestingly, fungal sensitization is more common in children and has been linked to severe asthma resulting in death. The accepted paradigm is that fungal sensitization occurs as a result of recurrent, transient environmental exposures. Yet, increasing evidence suggests that fungi may interact with people in unrecognized ways to promote asthma. My lab is interested in understanding the role of subclinical fungal infections in asthma and their potential contribution to the high prevalence of asthma in urban areas.
Cryptococcus neoformans is an encapsulated fungus that is well suited to serve as co-factor in urban asthma. C. neoformans colonizes pigeon droppings and is endemic to urban areas. Once inhaled, this fungus causes persistent, subclinical infections. We have demonstrated that the majority of Bronx children older than 2 years have serologic evidence of cryptococcal infection. Cryptococcal infection induces TH2 inflammation in animal models. In a rat model, we have shown that cryptococcal pulmonary infection acts a co-factor to enhance allergic inflammation to allergen challenge and promotes airway hyper-responsiveness, both hallmark features of asthma. Pulmonary cryptococcosis also induces chitinase expression, which has recently been implicated as an essential mediator of allergic inflammation.
To study this phenomenon, we have established collaborations with Pulmonary Medicine, Critical Care and Emergency Medicine at the ChildrenÃ¢â‚¬â„¢s Hospital of Montefiore. These collaborations provide access to the large number of children with asthma in the Bronx. Current studies underway include a characterization of chitinase expression among asthmatics and a comparison of cryptococcal infection prevalence among asthmatics and non-asthmatics. Animal experimentation directed at understanding the mechanisms and variables related to fungal induced asthma are also underway.
In addition to fungal studies, my lab is interested in anthrax pathogenesis. Bacillus anthracis is widely recognized as a potential agent of bioterrorism as evidenced by the 2001 anthrax attack. The toxins of B. anthracis are essential to virulence. In collaborations with Drs. Arturo Casadevall and Jurgen Brojatsch, we have studied the mechanisms by which Bacillus anthracis toxins contribute to host death. We have identified a previously unrecognized protease in human serum that inactivates the protective antigen component of lethal toxin in vitro. The precise protease and its role in the host response and susceptibility to anthrax remain to be determined. We have also identified a potential role for platelet activating factor (PAF) in mediating the lethal effects of toxin, including the alterations in vascular permeability which is characteristic of anthrax. Together, these observations may have important implications in developing new approaches to the treatment of anthrax.
Expert Opin Pharmacother. 2009 Aug 27. [Epub ahead of print]
PMID: 19708853 [PubMed - as supplied by publisher]:
Eukaryot Cell. 2009 Jul 17. [Epub ahead of print]
PMID: 19617395 [PubMed - as supplied by publisher]
Clin Infect Dis. 2009 Jun 15;48(12):1713-23. Review.
PMID: 19441978 [PubMed - indexed for MEDLINE]
Med Mycol. 2009 Apr 22:1-12. [Epub ahead of print]
PMID: 19384753 [PubMed - as supplied by publisher]
Am J Perinatol. 2009 Jan;26(1):89-91. Epub 2008 Nov 21. Review.
PMID: 19031357 [PubMed - indexed for MEDLINE]
Clin Pediatr (Phila). 2009 Jun;48(5):568-71. Epub 2008 Nov 21. No abstract available.
PMID: 19028931 [PubMed - indexed for MEDLINE]
Infect Immun. 2009 Jan;77(1):128-40. Epub 2008 Oct 27.
PMID: 18955480 [PubMed - indexed for MEDLINE]
Med Mycol. 2008 Aug;46(5):457-63. Epub 2008 Mar 10.
PMID: 18608912 [PubMed - indexed for MEDLINE]
Curr Opin Microbiol. 2008 Aug;11(4):313-7. Epub 2008 Jun 21. Review.
PMID: 18573683 [PubMed - indexed for MEDLINE]
Pediatr Neurol. 2008 Jul;39(1):63-6.
PMID: 18555177 [PubMed - indexed for MEDLINE]
Front Biosci. 2008 May 1;13:4009-14. Review.
PMID: 18508494 [PubMed - indexed for MEDLINE]
Respir Res. 2008 May 15;9:40.
PMID: 18482441 [PubMed - indexed for MEDLINE]
Clin Vaccine Immunol. 2008 Jun;15(6):970-3. Epub 2008 Apr 30.
PMID: 18448623 [PubMed - indexed for MEDLINE]
Pediatr Infect Dis J. 2008 May;27(5):468-9.
PMID: 18360300 [PubMed - indexed for MEDLINE]
Med Mycol. 2008 Mar;46(2):153-62.
PMID: 18324494 [PubMed - indexed for MEDLINE]
Clin Vaccine Immunol. 2007 Dec;14(12):1550-4. Epub 2007 Oct 24.
PMID: 17959819 [PubMed - indexed for MEDLINE]
Pediatr Infect Dis J. 2007 Jun;26(6):549-51.
PMID: 17529880 [PubMed - indexed for MEDLINE]
J Infect. 2007 Jun;54(6):521-9. Epub 2007 Jan 18. Review.
PMID: 17239952 [PubMed - indexed for MEDLINE]
J Infect Dis. 2006 Apr 15;193(8):1178-86. Epub 2006 Mar 9.
PMID: 16544260 [PubMed - indexed for MEDLINE]
Microbiology. 2006 Jan;152(Pt 1):3-9. Review.
PMID: 16385110 [PubMed - indexed for MEDLINE]
J Immunol. 2005 Nov 15;175(10):6757-63.
PMID: 16272332 [PubMed - indexed for MEDLINE]
J Immunol. 2005 Sep 1;175(5):3244-51.
PMID: 16116215 [PubMed - indexed for MEDLINE]
Infect Immun. 2005 Mar;73(3):1779-87.
PMID: 15731079 [PubMed - indexed for MEDLINE]
Pediatr Infect Dis J. 2003 Dec;22(12):1089-93. Review.
Infect Immun. 2003 Feb;71(2):930-6.
PMID: 12540575 [PubMed - indexed for MEDLINE]
Microbes Infect. 2002 Nov;4(13):1345-52. Review.
PMID: 12443899 [PubMed - indexed for MEDLINE]
Infect Immun. 2002 Sep;70(9):5177-84.
PMID: 12183568 [PubMed - indexed for MEDLINE]
Pediatrics. 2001 May;107(5):E66.
PMID: 11331716 [PubMed - indexed for MEDLINE]
Med Mycol. 2000;38 Suppl 1:79-86. Review.
PMID: 11204167 [PubMed - indexed for MEDLINE]
Persistent Cryptococcus neoformans pulmonary infection in the rat is associated with intracellular parasitism, decreased inducible nitric oxide synthase expression, and altered antibody responsiveness to cryptococcal polysaccharide.
Infect Immun. 2000 Feb;68(2):832-8.
PMID: 10639453 [PubMed - indexed for MEDLINE]
Infect Immun. 1999 Nov;67(11):6076-83.
PMID: 10531269 [PubMed - indexed for MEDLINE]
Infect Immun. 1999 May;67(5):2218-24.
PMID: 10225877 [PubMed - indexed for MEDLINE]
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14967-72.
PMID: 9843999 [PubMed - indexed for MEDLINE]
Antimicrob Agents Chemother. 1998 Jun;42(6):1437-46.
PMID: 9624491 [PubMed - indexed for MEDLINE]
J Infect Dis. 1998 Jun;177(6):1647-59.
PMID: 9607845 [PubMed - indexed for MEDLINE]
Pharmacokinetics and biodistribution of a monoclonal antibody to Cryptococcus neoformans capsular polysaccharide antigen in a rat model of cryptococcal meningitis: implications for passive immunotherapy.
J Med Vet Mycol. 1997 Jul-Aug;35(4):271-8.
PMID: 9292424 [PubMed - indexed for MEDLINE]
Lab Invest. 1996 Dec;75(6):759-70.
PMID: 8973471 [PubMed - indexed for MEDLINE]
Infect Immun. 1995 Sep;63(9):3448-53.
PMID: 7642276 [PubMed - indexed for MEDLINE]
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Golding Building, Room 702
Bronx, NY 10461