Driector Section of Immunololgy; Professor and Chair of Pediatrics

• Margaret Hostetter, Professor and Chair, Director, Division of Immunology
  Special Interests: Pathogenesis of pneumococcal and candidal infections

Non-Faculty members (technical, clerical)

• Denise Devore-Carter, Head technician, Hostetter lab
• Xiao dan Xhao, Research assistant, Hostetter lab
• Vincent Vellucci, Research Assistant, Hostetter lab
• Janet Watson, Administrative Assistant

Fellows and other trainees

• Scott Gygax, Postdoctoral associate
• Charlotte Frank, Graduate student

Current Grant Support

Name	Title	Funding Agency	Dates
R01 AI 45145	A Fibronectin Receptor in Candida tropicalis	NIH	3/1/99-2/28/04
R01 AI 50813	Biology of Int1p in Candida albicans Fungemia	NIH	7/1/02-6/30/07
R21 AI49149	C3-Binding and -Degrading Proteases in S. pneumoniae	NIH	8/1/02-7/31/03
#6 FY02 151	Role of a Candida albicans Super-antigen in Fungemia	March of Dimes	7/1/02-6/30/04
CR Bard, Inc.	Interactions of C. albicans with Heparin	Industry	1/15/03-1/14/04

Honors and Awards for 2001 and 2002:

• Hostetter, Maxwell Finland Lecture, IDSA-2001, Induction into the Institute of Medicine, 2001

Publications for 2001 and 2002:
Original reports:
Zhang, Y., Masi ,A.W., Barniak, V., Mountzouros, K., Hostetter, M.K., Green, B.A. Recombinant PhpA protein, a unique histidine-motif containing protein from Streptococcus pneumoniae, protects mice against intranasal pneumococcal challenge. Infect. Immun. 69:3827-3836, 2001.

McDonough, J.M., Bhattachergee, V., Sadlon, T., and Hostetter, M.K. Involvement of Candida albicans NADH dehydrogenase complex I in filamentation. Fungal Genetics and Biol. 36: 117-127, 2002.

Reviews and Chapters:
Hostetter, M.K. “Infectious Diseases in Internationally Adopted Children.” Textbook of Pediatric Infectious Diseases, R. Feigin and J. Cherry, editors; W.B. Sauunders, Philadelphia, 2001.

21st edition, Rudolph’s Textbook of Pediatrics. Abraham Rudolph, Colin Rudolph, editors. Margaret K. Hostetter, George Lister, Norman Siegel, associate editors (Hostetter edited sections on infectious diseases, immunology, rheumatology, orthopedics, and dermatology.)

Hostetter, M.K. Fungal Infections in the NICU”. Avery’s Diseases of the Newborn. M.E. Avery and W. Taeusch, editors., in press.

Research Interests and Activity
The focus of the Hostetter laboratory is to understand how pathogenic organisms evade host defenses to cause infection and injury. The yeast Candida albicans is the most frequent cause of life-threatening fungal infection in immunocompromised hosts. We have used molecular tools to dissect how C. albicans adheres to the epithelium of the gastrointestinal tract, breaches this barrier by forming invasive hyphae, and elicits the release of toxic cytokines from cells of immune surveillance. The gene INT1, identified in our laboratory, is unique to Candida albicans and is the first gene reported to link epithelial attachment, formation of invasive hyphae, and virulence [Science 279:1355-8, 1998]. Current studies are directed toward understanding how Int1p and other candidal proteins promote virulence in two specialized environmental niches: the bloodstream and the gastrointestinal tract.

The second organism of interest, Streptococcus pneumoniae, is the leading cause of death from respiratory infections the world over. Our laboratory has identified several pneumococcal genes encoding surface proteins that interfere with the opsonic function of C3. Two genes encode C3-degrading proteinases: one cleaves the C3 alpha chain and the other degrades the C3 beta chain. The third gene encodes a C3-binding protein that elicits IL-8 from respiratory epithelial cells. All three genes are conserved in geographically disparate isolates of S. pneumoniae. S. pneumoniae bearing mutations in these genes are killed much more readily than wild type strains. When expressed as recombinant antigens, the proteins encoded by these genes prevent colonization and bacteremia in murine models. These studies are contributing to the development of protein-based vaccines for S. pneumoniae.

Dr. Hostetter’s clinical interest focuses on the medical evaluation of internationally adopted children, a field which she pioneered in 1986 with colleagues from the University of Minnesota. Over the past 16 years she has evaluated more than 1500 internationally adopted children. Work at Minnesota and now at Yale has led to the development of screening tests now recommended by the American Academy of Pediatrics and to the founding of more than 30 international adoption clinics across the U.S.