Research

1. Susan Plaeger, Ph.D.

   We continued to make strides in understanding the immunologic and virologic factors involved in the vertical transmission of HIV infection through our NIH/NIAID RO1-funded research. A research article published in June in the Journal of Infectious Diseases, "Decreased CD8 cell mediated viral suppression and other immunologic characteristics of women who transmit HIV to their infants", was picked up for citation by the Reuters news service and the Infectious Disease Society Association newsletter. Two additional scientific research articles were published in 1999, three more were accepted for publication and three submitted. We also continued our work for the NIH/NIAID Pediatric AIDS Clinical Trials Group as one of 6 NIAID-funded Core Immunology Laboratories in the U.S. I continued to serve as a peer reviewer for both the NIH/NIAID and the Pediatric AIDS Foundation. Dr. Ulrike Ziegner completed postdoctoral work in the laboratory in December, and Dr. Thao Pham joined the laboratory from Yale in July as a postdoctoral fellow, having been awarded an NIH AIDS Training grant fellowship. I resigned in October 99 to assume a position at the NIH division of AIDS.

    

2. David Rawlings, M.D.

   Studies from my laboratory continue to define the signaling events mediating the sustained Ca2+ signal in mature and immature B cells folowing pre-B cell and B cell antigen receptor activation, respectively. This work is supported by an NIH RO1 award and a Career Development Award from the James S. McDonnell Foundation. We have developed a novel culture model for long-term growth and maturation of human B-progenitors including generation of mature immunoglobulin secreting B cells from highly purified multipotent human stem cells. This represents the first in vitro culture system capable of sustaining each of the human B lineage developmental stages from stem cell to mature B cell. This system is currently being utilized to evaluate gene therapy protocols and to study the growth requirement of hematopoietic stem cell populations and early B lineage cells including the role of the novel cytokine TSLP. Our group continues to make progress in B cell gene therapy projects demonstrating high level transfer of the cytoplasmic tyrosine kinase, Btk, into human and murine Btk-/- cell populations using both retroviral and lentiviral vectors. This latter work is supported by a second R01 award, and a Scholar Award from the Leukemia Society of America.

    

3. Dr. Robert Roberts, M.D., Ph.D.

   We are continuing a number of studies using human cord blood cells as a source of stem cells and progenitor cells for differentiation and expansion. One project will involve using cord blood cells from HIV infected infants that can undergo genetic transformation to make them more resistant to HIV infection. This work is supported in part by the ACTG and the Pediatric AIDS Foundation. We are also involved in studies using cytokines, primarily interleukin-15, to expand and activate NK cells (and their progenitors) from newborns (cord blood) and HIV patients. We have found that Il-15 will maintain NK cells in culture up to 10 weeks and will expand the number of NK cells up to 100 fold. Another area of research involves the effects of albuterol isomers on eosinophils, and we are applying for funding from pharmaceutical companies to support this work. We have four students in our lab supported by grants from the Pediatric AIDS Foundation, the UCLA Academic Senate, and the Student Research Project. We are also involved in clinical study with the Fujisawa Company to study the effects of topical tacrolimus in the treatment of atopic dermatitis.

    

4. E. Richard Stiehm, M.D.

   I served as PI and Co-PI of two nationwide ACTG studies of Hyperimmune HIV-IVIG to treat HIV and prevent maternal-foetal HIV transmission. Six manuscripts have been published or in press from this work. I also co-authored a study on the use of IVIG in asthma. I have assumed the directorship of the ACTG core lab following the resignation of Dr. Plaeger. Clinical studies of Tacrolimus ointment in eczema and efficacy studies of new IVIG preparations are planned. I was on sabbatical at Great Ormond Street Hospital of London from 6/1 to 10/1/99.

    

5. Christel H. Uittenbogaart, M.D.

   Understanding the interaction between HIV and the developing T cell in the thymus continues to be the main focus of the laboratory. During the past year we finished studies of co-receptor use by viral isolates obtained from HIV-infected infants. Our findings show that CCR5 is used as co-receptor by 80% of primary isolates despite the low level of CCR5 expression (less than 1%) in the thymus. Tropism for CCR5 was observed in HIV isolates obtained close to or at birth from infants infected in utero or intrapartum, regardless of their disease progression profile (manuscript submitted). Significant progress has been made in the following projects: mechanisms of regulation of HIV expression in thymocytes by cytokines; elucidation of host factors affecting viral entry and post-entry events in thymocyte subsets. In our search to determine factors involved in maintaining normal T cell differentiation in the pediatric thymus we found that postnatal thymic organ culture can be used to study T cell differentiation and that migration of T cell precursors into the thymus is intact in postnatal specimens. In addition, we have shown that a change in thymocyte subsets negatively affects differentiation of T cell precursors in the thymus and that cytokines normally present in the thymus affect T cell regeneration. In collaboration with Dr. Hergen Spits in The Netherlands we are defining the development and role of dendritic cells of lymphoid origin (DC2) in the thymus. All studies are done in a three-dimensional model comprised of in vitro thymocyte suspension culture, thymic organ culture and in vivo using the SCID-hu mouse model. The results of these studies have direct implications for HIV pathogenesis in pediatric patients.

Faculty Profiles

PLAEGER, SUSAN

Faculty Member Since:	1985
Degrees:	PhD, MS, Louisiana State University Medical Center, New Orleans BS, Loyola University
Rank:	Adjunct Associate Professor
Grant Support:	1991-2001 PHS National Institute of Allergy & Infectious Diseases 1996-99 NIH-NIAID 1997-2001 NIH/NIAID R01 1997-2001 NIH/NIAID

RAWLINGS, DAVID J.

Faculty Member Since:	1996
Degrees:	MD, University of North Carolina, Chapel Hill BS, Davidson College, Magna Cum Laude
Rank:	Assistant Professor
Research Interests:	B cell development and signal transduction B lineage gene therapy Role of dysregulated B cell signal transduction in autoimmunity
Grant Support:	97-2000 James S. McDonnell Scholar Award 98-1999 CHRC, HHMI, and Pennington Faculty Research Awards UCLA 98-1999 Joan Drake Seed Grant for Excellence in Cancer Research UCLA 98-2003 NIH 1RO1 HD37091, NICHD
Teaching:	Rheumatology Grand Rounds Core lectures to third year students Round on Immunology service Rheumatology clinic teaching of Allergy/Immunology/Fellows Students and Adult Rheumatology Fellows
University Service:	Committee for Internal Review of Biomedical Studies (CIRBS) UCLA, Multipurpose Arthritis and Musculoskeletal Disease Center (MAMDC) Review for Committee for UCLA Gene Therapy Research Grants Reviewer for Jonsson Comprehensive Cancer Center Research Grants UCLA MSTP Review/Admissions Committee UCLA Patent Advisory Panel
Outside Activities:	Ad hoc reviewer for Blood, Exp. Hematology J. Clinical Investigation, Immunology, EMBO Journal, PNAS, Clinical Immunology
Honors	McDonnell Scholar Award Leukemia Society Scholar Award

ROBERTS, ROBERT L.

Faculty Member Since:	1988
Degrees:	PhD, MD, BA, Emory University
Rank:	Assistant Clinical Professor
Research Interests:	Natural Killer cells, cytokine therapy, AIDS and granulocyte disorders
Grant Support:	Pediatric AIDS Foundation, ACTG, and various other grants to students in lab, Sepracor, Inc. _ Pilot study on the effects of albuterol isomers on eosinophils
Teaching:	In-house attending, Olive View Allergy Clinic, Medical Student Core Lectures, Joint Adult/Pediatric Conference preparing series of presentations on asthma/allergy for patient education.

STIEHM, E. RICHARD

Faculty Member Since:	1969
Degrees:	MD, BS, University of Wisconsin-Madison
Rank:	Professor, Division Chief
Research Interests:	Use of Immune Globulin, Cytotoxic Responses, HIV Clnical Trials
Grant Support:	ACTG (Co-Investigator) ACTG Core Lab (PI) World AIDS Association (PI)
Teaching:	Fellows, Medical Students, Residents
University Service:	Member, Council of Academic Personnel Member, CRC Advisory Committee
Professional Committees:	AIDS ClinicalTrial Group _ Multiple Committees Pediatric AIDS Foundation _ Advisory Board Immune Deficiency Foundation, Chair- Blood Derivatives Committee
Honors:	UCLA Medical Alumni Science Award Babies Hospital, (NYC), Distinguished Alumnus Award

UITTENBOGAART, CHRISTEL H.

Faculty Member Since:	1986
Degrees:	MD, University of Leiden (The Netherlands)
Rank:	Adjunct Professor
Research Interests:	Understanding the interaction between HIV and the developing T cell in the thymus, the expression of chemokine receptors on thymocytes at different stages of maturation, the effects of HIV isolates on T cell development using virus obtained from patients with either rapid or slow disease progression.
Grant Support:	1996-01 NIH/HD Analysis of HIV Infection of the Pediatric Thymus 1998-99 NIH/HL Cytokine Therapy for HIV Infection in Vivo 1998-00 NIH/HD T cell development in the postnatal thymus 1998-00 NIH/PAS Immune reconstitution: HIV-infected infants post HAART
Teaching:	Immunology Forum (M260) Ethics in Science Course (M234) Postdoctoral fellows, graduate students and medical students
University Service:	Co-Chair of UCLA AIDS Institute Grant Review Committee Member, Immunology Forum Committee Member, Revlon/UCLA Breast Center Research Committee
Professional Committees:	Executive Director of the Midwinter Conference of Immunologists. Scientific Advisory Committee of the Pediatric AIDS Foundation

Division Publications

1. Dovat S, Wakim M, Roberts RL, Stiehm ER, and Feig SA. Immune thrombocytopenia after umbilical cord progenitor cell transplant: Response to Vincristine. Bone Marrow Transplant 24:321-323, 1999.
2. Dreimane D, Gallagher K, Nielsen K, Krogstad P, Stiehm ER, Bryson YJ, and Geffner ME. Growth hormone exerts potent anabolic effects in an adolescent with HIV wasting. Ped Infect Dis J. 18:167-169, 1999.
3. Goldman, FD, Gilman AD, Hollenback C, Kato RM, Premack BA, Rawlings DJ. Hydroxychloroquine inhibits calcium signals in T cells, a new mechanism to explain its immunomodulatory properties. Blood (In Press) 1999.
4. Kishiyama JL, Valacer D, Cunningham-Rundles C, Sperber K, Richmond GW, Abramson S, Glovsky M, Stiehm ER, Stocks J, Rosenberg L, Shames RS, Corn B, Shearer WT, Bacot B, DiMaio M, Tonetta S and Adelman DC. A multicenter, randomized, double blind, placebo-controlled trial of high-dose intravenous immunoglobulin for oral corticosteroid-dependent asthma. Clin Immunol. 91:126-133, 1999.
5. Krogstad P, Uittenbogaart CH, Dickover R, Bryson YJ, Plaeger S and Garfinkel A. Primary HIV infection of infants: the effects of somatic growth on lymphocyte and virus dynamics. Clinical Immunology. 92: 25-33, 1999.
6. Lambert JS, Watts DH, Mofenson L, Stiehm ER, Bethel J, Whitehouse J, Jimenez E, Gandia J, Scott G, O Sullivan MJ, Kovacs A, Stek S, Shearer W, Hammill W, Van Dyke R, Maupin R, Silio M, Fowler MG, MPH for the Pediatric AIDS Clinical Trials Group 185 Team: Risk Factors for Preterm birth and low birth weight in infants born to HIV-infected pregnant women receiving Zidovudine. J. AIDS (In Press) 1999.
7. Ming JE, Stiehm ER and Graham JM. Syndromes associated with immunodeficiency, in Advances in Pediatrics, Edited by Barness L. 46:271-328, 1999.
8. Mofenson LM, Lambert JS, Stiehm ER, Bethel J, Meyer WA, Whitehouse J, Moye J Jr., Reichelderfer P, Harris DR, Nugent R, Fowler MG, Mathieson BJ, Nemo GJ, for the PACTG 185 Team: Risk factors for perinatal transmission of Human Immunodeficiency Virus Type 1 in women treated with Zidovudine. New Engl J. Med 341: 385-393, 1999.
9. Plaeger S, Bass HZ, Nishanian P, Thomas J, Aziz N, Detels R, King J, Cumberland W, Kemeny M, Fahey JL. The prognostic significance in HIV infection of immune activation represented by cell surface antigen and plasma activation marker changes. Clin Immunol 90:238046, 1999.
10. Plaeger S, Bermudez, Mikyas Y, Harawa N, Dickover R, Mark D, Dillon M, Bryson YJ, Boyer P, Sinsheimer JS. Decreased CD8 cell-mediated viral suppression and other immunologic characteristics of women who transmit human immunodeficiency virus to their infants. J. Infect Dis 179:1388-94, 1999.
11. Rawlings DJ. Bruton's tyrosine kinase controls a sustained calcium signal essential for B lineage development and function. Clinical Immunology 91:243-254, 1999.
12. Roberts RL and Stiehm ER. Immunodeficiency, in Encyclopedia of Life Sciences, Nov 1998. MacMillan (In Press) 1999.
13. Roberts RL. Ammann AJ, and Stiehm ER. Phagocyte Immunodeficiency Disorders, in Stites DP, Terr A, and Parslow TG. Editors, Medical Immunology, Edition 10, Appleton and Lange (In Press) 1999.
14. Roberts RL. and Stiehm ER. Immunodeficiency. Encyclopedia of Life Sciences. (In Press) 1999.
15. Roberts RL. Ammann AJ, and Stiehm ER. Mechanisms in immunodeficiency in Stites DP, Terr A, and Parslow TG. Editors, Medical Immunology Edition 10, Appleton and Lange (In Press) 1999.
16. Roberts RL. Infections in natural immunodeficient hosts. Pediatric Infectious Diseases. Churchill-Livingstone, Philadelphia, pp. 16.1-16.18, 1999.
17. Roberts RL. Seasonal Effects of Asthma. J. Resp. Care Practioners, 12:45-48, 1999.
18. Schmid I, Ferbas J, Uittenbogaart CH, and Giorgi JV. Flow cytometric analysis of live cell proliferation and phenotype in populations with low viability. Cytometry 35:64-74, 1999.
19. Schuster V, Seidenspinner S, Zeitler P, Escher C, Pleyer U, Bernauer W, Stiehm ER, Isenberg S, Mingers A-M, Schambeck C, and Kreth WH. Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis. Proposal of a third type of plasminogen deficiency. Blood 93:3457-3466, 1999.
20. Stiehm ER and Keller MA. Breast Milk Transmission of Viral Disease, in The Immunological Properties of Milk. Edited by Woodward W and Draper HH. Advances in Nutritional Research Vol. 10. Plenum Press, New York, 2000 (In Press) 1999.
21. Stiehm ER. Book Review: Adolescent Rheumatology, edited by Isenberg DA and Miller JJ III Dunitz, 1999, in New Engl J. Med 340: 1846, 1999.
22. Stiehm ER, Ammann AJ, and Roberts RL. (Cellular) T-Cell immunodeficiency disorders, in Stites DP, Terr A, and Parslow TG. Editors, Medical Immunology, Edition 10, Appleton and Lange (In Press) 1999.
23. Stiehm ER, Fletcher CV, Mofenson LM, Palumbo PE, Kang M, Fenton T, Sapan CV, Meyer III WA, Shearer WT, Hawkins E, Fowler MG, Bouquin P, Purdue L, Sloand E, Nemo GJ. Wara D, Bryson YJ, Starr SE, Petru A and Burchett S. for the Pediatric AIDS Trials Group Protocol 273 Study Group: Use of HIV-IVIG in HIV-1 infected children (PACTG 273) . J. Inf. Diseases. (In Press) 1999.
24. Stiehm ER, Lambert JS, Mofenson LM, Bethel J, Whitehouse J, Nugent R, Moye J Jr., Fowler MG, Mathieson BJ, Reichelderfer P, Nemo GJ, Korelitz J, Meyer WA, Sapan CV, Jimenez E, Gandia J, Scott G, O'Sullivan MJ, Kovacs A, Stek A, Shearer WT, and Hammill H. for the Pediatric AIDS Clinical Trials Group Protocol 185 Team. Efficacy of Zidovudine and HIV hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced HIV disease: Results of pediatric AIDS clinical trials group protocol 185. J Inf Dis. 179:567-575, 1999.
25. Stiehm ER. Mothers, Babies and AIDS _ UCLA Magazine, p20-22, June 1999.
26. Stiehm ER, Roberts RL, and Ammann AJ. Antibody (B-Cell) immunodeficiency disorders, in Stites DP, Terr A, and Parslow TG. Editors, Medical Immunology, Edition 10, Appleton and Lange (In Press) 1999.
27. Stiehm ER, Roberts RL, and Ammann J. Combined antibody (B-Cell) and Cellular (T-cell) Immunodeficiency Disorders, in Stites DP, Terr A, and Parslow TG. Editors Medical Immunology, Edition 10 , Appleton and Lange (In Press) 1999.
28. Stiehm ER. Conventional Therapy of Primary Immunodeficiency Diseases, in Primary Immunodeficiency Diseases, A Molecular and Genetic Approach. Edited by Ochs HD, Smith CIE, and Puck JM. Oxford U. Press, Oxford UK, pp. 448-458, 1999.
29. Stiehm ER. Immune Globulin Therapy, in Transfusion Therapy: Clinical Principles and Practice. Edited by Mintz PD. AABB Press. Bethesda MD, pp. 267-290, 1999.
30. Stiehm ER. Immunodeficiency Diseases, in Merck Manual Edition 17, Edited by Beers MH and Berkow R. Merck Research Laboratories, Whitehouse Station NJ pp. 1023-1049, 1999.
31. Stiehm ER. Book Review: Adolescent Rheumatology, edited by Isenberg DA and Miller JJ III Dunitz, 1999, in New Engl J. Med 340: 1846, 1999.
32. Stiehm ER. Editorial: Cytokine Dysregulation in the Hyper-IgE Syndrome. J. Pediatr. (In Press) 1999.
33. Watts DH, Lambert J, Stiehm ER, Bethel J, Whitehouse J, Fowler MG, and Read J: Complications according to mode of delivery among HIV-infected women with CD4-Lymphocyte counts of 500 or less. Amer. J Obstet. Gynec. 2000 (In Press) 1999.