Toxoplasmosis Center:

Research Programs
 Research on Toxoplasmosis at the University of Chicago: Basic, Translational, Clinical


Some Members of the McLeod Laboratory
(In the Research Laboratory, Summer 2006)

Our work is focused on the biology of the parasite, developing better medicines to eliminate the parasite, genetics of susceptibility and resistance (host, parasite and their interaction), and understanding the immune responses directed against the parasite and how they might be stimulated to prevent toxoplasmosis.
 


Other Members of the McLeod Research Group
(Determining Toxoplasmosis susceptibility and resistance genes, Winter, 2007)

 

These are examples of the questions and problems our investigators study.

1) Understanding inhibition of unique molecular targets that would facilitate creating medicines that eliminate all life cycle stages of the parasite. This is especially important so that disease recurrence is not an issue and treatments are easier to administer, of shorter duration and curative.

2) Developing a vaccine that prevents acquisition and congenital transmission of Toxoplasma gondii.

3) Understanding how Toxoplasma causes infection, whether host genes influence that process, and if so, how.

4) Determining whether persistence of this parasite in the brain and eye leads to sequelae later in life.

5) Evaluating the intermediate and long-term cognitive, neurologic, ophthalmologic, and audiologic outcomes for individuals with treated congenital toxoplasmosis.

6) Determining whether there are late side effects associated with treatment.


These are some of the scientific discoveries our investigators have made.

1) Discovery of susceptibility and resistance genes for toxoplasmosis in mice and humans, and mechanisms whereby they have these effects.

2) Development of models to assess vaccine efficacy and novel approaches to vaccines effective in prevention of toxoplasmosis.

3) Immunization of mice that reduces parasite burden, improves outcomes for adult mice and reduce congenital infection in mice.

4) Unique metabolic pathways and their products, and organelle targeting in apicomplexan parasites which comprise antimicrobial targets not present in animals and inhibitors of these pathways.

5) Novel means to deliver small molecules effective against parasites across multiple membranes, into cells, and active and latent parasites.

6) Development of lead anti-Toxoplasma inhibitory compounds using a structure based-rational design approach woth crystallography and medicinal chemistry collaborators.

7) Lipidomics analysis of T.gondii, with collaborators.

8) Maternal inheritance of the T.gondii plastids, in collaboration with other scientists.

9) Potential improved treatments for toxoplasmosis.

10) Treatments for human congenital toxoplasmosis that are now the established means for treating this disease and that result in improved cognitive, motor, hearing and vision outcomes for afflicted infants, children, and adults.

 

Arom in T. gondii


Novel plant-like metabolic pathways; medicine targets


HLA supermotif bound peptide; the basis for a vaccine


Delivery into Bradyzoite


HLA DQ3 is a susceptibility allele


Representative Publications

Immunology, Genetics, and Vaccines

Brown C, C David, S Khare, and R McLeod. Effect of Human MHC Class I Transgenes on T. Gondii Cyst Formation. Journal of Immunology. 152: 4537-4541, 1994.

Brown C, C Hunter, R Estes, E Beckmann, J Forman, C David, JS Remington, and R McLeod. Definitive Identification of a Gene that Confers Resistance Against Toxoplasma Cyst Burden and Encephalitis. Immunology. 85: 419428,
1995.

Johnson JJ, Y Suzuki, D Mack, E Mui, R Estes, C David, E Skamene, J Forman, and R McLeod. Genetic Analysis of Influences on Survival Following Toxoplasma Gondii Infection. International Journal for Parasitology. 31: 109-113, 2001.

Johnson J, CW Roberts, C Pope, F Roberts, M Kirisits, R Estes, E Mui, T Krieger, C Brown, J Forman, and R McLeod. In Vitro Correlates of Ld Restricted Resistance to Toxoplasmic Encephalitis and their Critical Dependence on Parasite Strain. Journal of Immunology. 169: 966-973, 2002.

Kirisits M, E Mui, and R McLeod. Measurement of the Efficacy of Vaccines and Antimicrobial Therapy Against Infection with Toxoplasma Gondii. International Journal for Parasitology. 30: 149-155, 2000.

Mack D, J Johnson, F Roberts, C Roberts, R Estes, C David, C Grumet, R Estes, and R McLeod. Hla-class II Genes Modify Outcome of Toxoplasma Gondii Infection (Rapid Communication). International Journal for Parasitology. 29: 1351-1358, 1999.

McLeod R, J Frenkel, R Estes, D Mack, P Eisenhauer, and G Gibori. Subcutaneous and Intestinal Vaccination with Tachyzoites of Toxoplasma Gondii and Acquisition of Immunity to Peroral and Congenital Toxoplasma Challenge. Journal of Immunology. 140: 1632-1637, 1988.

Molecular Targets and Novel Medicines and Delivery

Muench SP, JB Rafferty, R McLeod, DW Rice, and ST Prigge. Expression, Purification, and Crystallization of the Plasmodium Falciparum Enoyl Reductase. Acta Crystalog. D59: 1246-1248, 2003.

Mui E, D Jacobus, WK Milhous, G Schiehser, H Hsu, CW Roberts, M Kirisits, and R McLeod. Triazines Inhibit Toxoplasma Gondii Tachyzoites in vitro and in vivo. Antimicrobial Agents and Chemotherapy. 49 (8): 3463-3467, 2005.

Samuel BJ, B Hearn, DG Mack, P Wender, J Rothbard, M Kirisits, E Mui, C Roberts, S Prigge, D Rice, SP Muench, A Law, and R McLeod. Delivery of Antimicrobials into Parasites. PNAS. Nov 25; 100 (24): 14281-14286, 2003.

Zuther E, JJ Johnson, R Haselkorn, R McLeod, and P Gornicki. Growth of Toxoplasma Gondii is Inhibited by Aryloxyphenoxypropionate Herbicides Targeting Acetyl-coa Carboxylase. PNAS. USA. 96: 13387-13392, 1999.

Other Basic Science

Campbell SA, TA Richards, E Mui, BU Samuel, JR Coggins, R McLeod, and CW Roberts. Rapid Communication: A Complete Shikimate Pathway in Toxoplasma Gondii: an Ancient Eukaryotic Innovation. International Journal of Parasitology. 34: 5-13, 2004.

Ferguson DJP, FL Henriquez, M Kirisits, S Muench, ST Prigge, DW Rice, CW Roberts, and R McLeod. Maternal Inheritance and Stage Specific Variation of the Apicoplast in Toxoplasma Gondii During Development in the Intermediate and Definitive Host. Eukaryotic Cell. 4 (4): 814-26, 2005.

Henriquez FL, MB Nickdel, R McLeod, RE Lyons, K Lyons, JF Dubremetz, ME Grigg, BU Samuel, and CW Roberts. Toxoplasma Gondii Dense Granule Protein 3 (GRA3) is a Type I Transmembrane Protein that Possesses a Cytoplasmic Dilysine (KKXX) Endoplasmic Reticulum (ER) Retriev al Motif. Parasitology. 131 (2): 1-11, 2005.

Richards T, J Dacks, S Campbell, J Blanchard, P Foster, R McLeod, and C Roberts. Ev olutionary Origins of the Eukaryotic Shikimate Pathway: Gene Fusions, Horizontal Gene Transfer, and Endosymbiotic Replacements. Eukaryotic Cell. 2006 Sep; 5 (9): 1517-1531.

Roberts F, CW Roberts, J Johnson, DE Kyle, T Krell, JR Coggins, GH Coombs, WK Milhous, S Tzipori, DJP Ferguson, D Chakrabarti, and R McLeod. Ev idence for the Shikimate Pathway in Apicomplexan Parasites. Nature. 393: 801-805, 1998.

Clinical Studies

Boyer K, E Holfels, N Roizen, C Swisher, D Mack, J Remington, S Withers, P Meier, T Karrison, and R Mcleod. Risk Factors for Toxplasma Gondii Infection in Mothers of Infants with Congenitial Toxoplasmosis: Implications for Prenatal Management and Screening. American Journal of Obstetrics and Gynecology. 192: 564-571, 2005.

McAuley J, K Boyer, D Patel, M Mets, C Swisher, N Roizen, C Wolters, L Stein, M Stein, W Schey, J Remington, P Meier, D Johnson, P Heydeman, E Holfels, S Withers, D Mack, C Brown, D Patton, and R McLeod. Early and Longitudinal Ev aluations of Treated Infants and Children and Untreated Historical Patients with Congenital Toxoplasmosis: The Chicago Collaborativ e Treatment Trial. Clinical Infectious Disease. 18: 38-72, 1994.

McLeod R, A Khan, and K Boyer. Sev ere Sulfadiazine Hypersensitiv ity in a Child with Reactiv ated Congenital Toxoplasmic Chorioretinitis. Pediatric Infectious Disease Journal. 2006 March; 25 (3): 270-272.

McLeod R, D Mack, K Boyer, M Mets, N Roizen, C Swisher, D Patel, E Beckmann, D Vitullo, D Johnson, and P Meier. Phenotypes and Functions of Lymphocytes in Congenital Toxoplasmosis. Journal of Laboratory Clinical Immunology. 116: 623-635, 1990.

McLeod R, K Boyer, T Karrison, K Kasza, C Swisher, N Roizen, J Jalbrzikowski, J Remington, P Heydemann, A Noble, M Mets, E Holfels, S Withers, P Latkany, P Meier, and the Toxoplasmosis Study Group. Outcome of Treatment for Congenital Toxoplasmosis, 1981-2004: The National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. Clinical Infectious Disease. 2006 May 15; 42 (10): 1383-1394.

Mets M, E Holfels, K Boyer, C Swisher, N Roizen, L Stein, M Stein, J Hopkins, S Withers, D Mack, R Luciano, D Patel, J Remington, P Meier, and R McLeod. Eye Manifestations of Congenital Toxoplasmosis. American Journal of Ophthalmology. 122: 309-324, 1996.

Patel D, E Holfels, N Vogel, K Boye, M Mets, C Swisher, N Roizen, L Stein, M Stein, J Hopkins, D Mack, R Luciano, P Meier, J Remington, S Withers, and R McLeod. Resolution of Intracranial Calcifications in Infants with Treated Congenital Toxoplasmosis. Radiology. 199: 433-440, 1996.

Roizen N, K Kasza, T Karrison, M Mets, AG Noble, K Boyer, C Swisher, P Meier, J Remington, J Jalbrzikowski, R McLeod, M Kipp, P Rabiah, D Chamot, R Estes, S Cezar, D Mack, L Pfiffner, M Stein, B Danis, D Patel, J Hopkins, E Holfels, L Stein, S Withers, A Cameron, J Perkins, and P Heydemann. Impact of Visual Impairment on Measures of Cognitive Function for Children with Congenital Toxoplasmosis: Implications for Compensatory Intervention Strategies. Pediatrics. 2006 August; 118 (2): e379-390.

Toxoplasmosis Clinical Center

Our goal is to better understand, prevent, and treat toxoplasmosis in children and people of all ages in Chicago and in many parts of the world.

This is accomplished in the Toxoplasmosis Clinical Center. In this Center, specialists from the University of Chicago provide comprehensive evaluations and expert care.

Row 1: Rima McLeod, MD, University of Chicago; Kenneth Boyer, MD, Rush University and Rush Presbyterian St. Luke’s Medical Center, University of Chicago; John Marcinak, MD, University of Chicago; James McAuley, MD, Rush University and Rush Presbyterian St. Luke’s Medical Center, University of Chicago; Charles Swisher, MD, Northwestern University, Children’s Memorial Hospital, University of Chicago; Peter Heydemann, MD, Rush University and Rush Presbyterian St. Luke’s Medical Center, University of Chicago.

Row 2: Michael Msall, MD, University of Chicago; Dianna Bardo, MD, Univeristy of Chicago; David McLone, MD, Northwestern University, Children’s Memorial Hospital; Gwen Noble, MD, University of Chicago; Paul Latkany, MD, New York Eye and Ear Hospital, New York University, Roosevelt Hospital, University of Chicago; William Mieler, MD, University of Chicago; Jack Remington, MD, Stanford University, Palo Alto Research Institute, University of Chicago.

Row 3: Kenneth Thompson, PhD, University of Chicago; Jeanne Perkins, MS, University of Chicago; Colette Gatling, PhD, University of Chicago; Andrew Suth, PhD, University of Chicago; Shawn Withers, RN, University of Chicago; Nancy Roizen, MD, Cleveland Clinic.

Row 4: Richard Penn, MD, University of Chicago; LouAnn Goldstein, MS, University of Chicago; Michael Kipp, MD, University of Chicago; Mark Greenwald, MD, University of Chicago; Mike Grassi, University of Chicago; Toria Trendler, BS, University of Chicago; Mari Sautter, BA, University of Chicago.

Toxoplasmosis Research Institute; Administrative Structure

Board of Directors

The Board of Directors consists of 15 members including: public advisors, scientists, physicians, a biostatistician, and legal counsel.

 
Rima McLeod
President
Clinical and Scientific Affairs

Dr. McLeod is the Jules and Doris Stein Research to Prevent Blindness Professor at the University of Chicago. She specializes in infectious diseases, especially toxoplasmosis, and studies pathogenesis, prevention, and treatment of toxoplasmosis and related diseases. She trained at the University of California, San Francisco and the University of Pennsylvania and was a Fellow in Infectious Diseases at Stanford University.
 
Kenneth Boyer
Chairman of the Board
Clinical Affairs

Dr. Boyer is the Chairman of Pediatrics and Pediatric Infectious Diseases at Rush University Medical Center in Chicago, IL. He studies treatment of congenital toxoplasmosis and prevention of group B streptococcal disease. Dr. Boyer trained at the University of Pennsylvania and was a fellow at the University of California, Los Angeles.
 
Paul Meier
Co-Treasurer
Dr. Meier currently teaches in the Department of Statistics at Columbia University in New York, NY, where he continues to make important contributions to the methods used for, and practice of, clinical trials. He is one of the Biostatisticians in the National Collaborative / Congenital Toxoplasmosis Treatment Study. He received his PhD in statistics from Princeton University in 1951. During his 5 years at John Hopkins, Dr. Meier worked in conjunction with E.L. Kaplan to create the Kaplan Meier analyses.
 
Laura Cussen
Co-Treasurer
Ms. Cussen is a co-treasurer. She has an MBA in Finance from DePaul University in Chicago, IL and has worked in banking for over 20 years, most currently as a VP in Treasury Services at JPMorgan Chase. She is especially interested in better treatments for toxoplasmosis as well as creating awareness of and preventing toxoplasmosis.
 
David Saperstein
Chairman
Business Affairs Committee
Educational Affairs

Mr. Saperstein is one of the public advisors for the institute. He is the founder and Chairman of Five S Capital, Ltd., a Houston-based partnership that specializes in strategic investments and is engaged in a number of diverse enterprises. David Saperstein is currently the Chairman of Tree Town USA, the largest container tree farm nursery in the world, and he was the founder, past Chairman and Chief Executive Officer of Metro Networks, Inc., the largest supplier of local content to the broadcast industry. Mr. Saperstein has also been involved in many children’s charities over the years and has received the highest Civilian Award given by the US Marine Corps for his work with Toys for Tots.
 
Janet Morel
Chairperson
Educational Affairs

Ms. Morel is one of the public advisors for the institute. She has appeared as a guest speaker for numerous workshops and seminars on disability awareness including the Dr. Dean Edell show. She has written a book on toxoplasmosis for parents entitled "Playing the Hand that's Dealt to You".
 
Fiona Forward
Business Affairs
Educational Affairs Committee

Ms. Forward is one of the public advisors. She has considerable interest in developing educational programs about toxoplasmosis and better treatments for the prevention of toxoplasmosis.
 
Trisha Rooney Alden
Business Affairs Committee
Ms. Rooney Alden is President, Founder, and majority owner of R4 Services, LLC, a full-service information management company. R4 has grown to be a leader in the records management industry largely due to its commitment to the highest standards of quality and customer service. Ms. Rooney Alden is involved in a variety of organizations including: member of the Visiting Committee to the Division of the Biological Sciences and the Pritzer School of Medicine at the University of Chicago, member of the Board of Trustees of the Francis Xavier Warde School, member of Old St. Patrick’s Church Parish Council, member of the Northwestern University Women’s Board, member of the President’s Council for Denison University, and member of The Economic Club of Chicago. Ms. Rooney Alden received her B.A. from Denison University.
 
Charles Swisher
Clinical Affairs
Dr. Swisher specializes in child neurology at the Children's Memorial Hospital in Chicago, Illinois. He is also the Pediatric Neurologist for the National Collaborative Toxoplasmosis Treatment Trial currently being carried out at the University of Chicago, and an associate professor of Pediatrics and Neurology at Northwestern University’s Feinberg School of Medicine. He trained at the McGill University Faculty of Medicine in Montreal, Canada and completed his postgraduate training at Washington University School of Medicine.
 
Nancy Roizen
Clincal Affairs
Dr. Nancy Roizen was a Professor of Pediatrics at the University of Chicago from 1985 through 2002. She recently relocated to Syracuse, New York where she is currently a Professor of Pediatrics and Psychiatry at Upstate University. Dr. Roizen received both her B.S. and M.D. from Tufts University followed by Residency at Johns Hopkins Medical Center.
 
Jeffrey Zorek
Business Affairs Committee
Education Affairs

Mr. Zorek is one of the public advisors. He is currently the Managing Director of Equity Capital Markets at Lehman Brothers in New York City.
 
Douglas Palonder
Business Affairs Committee
Educaton Affairs

Mr. Palonder is a Chicago native who holds multiple degrees from Youngstown State University: a Bachelor’s degree in Psychology/Sociology, a Bachelor of Science degree in Secondary Education, an Associate Degree in Nursing, and a Bachelor of Science Degree in Nursing. He later received his Master of Science degree in Health Management. In 1989 he opened his own insurance practice, Main Street Insurors. He is currently a Rotary District Governor in Pinellas County, Florida, one of 530 across the world that help guide 1.2 million members in 170 countries.
 
Mark Rust
Legal Counsel
Mark Rust, JD, is the managing partner of the Chicago office of Barnes & Thornburg, and the chair of its healthcare department. His practice is focused primarily on the representation of physician organizations, associations, and healthcare entities throughout the country. He regularly addresses organizations on current topics in health care law and frequently argues before the US Supreme Court.
 
Lloyd Kasper
Scientific Affairs
Dr. Kasper is Professor of Medicine (Neurology) and Microbiology at Dartmouth Medical School in Hanover, New Hampshire. He studies immunology of and immunopathology in Toxoplasma infections. He trained at the University of Illinois and completed his post graduate training at Rush Medical College in Chicago, Illinois.
 
Ben Stark
Scientific Affairs
Dr. Stark is a Professor of Biology at The Illinois Institute for Technology specializing in the study of the molecular biology, biochemistry and physiology of respiration in bacteria. He discovered RNaseP. Currently, his laboratory studies the hemoglobin and terminal respiratory cytochrome of the bacterium Vitreoscilla, and genetically engineers useful bacteria with the Vitreoscilla hemoglobin gene to improve their performance in applications such as bioremediation and production of biofuels. He received his undergraduate degree from the University of Michigan and completed his post graduate work at Yale University.

TRI Founding Goals

The Toxoplasmosis Research Institute (TRI) is a 501c3 not-for-profit organization dedicated to supporting research, education, and patient care for toxoplasmosis. TRI was formed in August of 1991. The specific goals of the foundation are:


1) To foster, promote, develop, perform, and encourage research on, and identification, treatment, and cure of toxoplasmosis and related diseases.

2) To invest and solicit funds and receive gifts and contributions for the charitable, scientific, and educational purposes of the corporation.

3) To develop public education programs to provide information about toxoplasmosis, including scientific research on toxoplasmosis, the prevention, care and treatment of toxoplasmosis, and to inform the public of programs that are available for the care and treatment of toxoplasmosis to those affected.

4) To provide financial assistance to those persons afflicted with toxoplasmosis who have financial needs related to their medical care.

5) To review and process grant applications and administer the expenditure of such grant funds consistent with the purposes and goals of the corporation.

6) To create, establish, manage, support, and administer trusts, grants, contracts, and endowments, and appropriate the income and principal thereof for the benefit, support, improvement, upkeep, expansion, replacement, and operation of the corporation and its programs.

7) To invest in for-profit activities not inconsistent with the purposes of the corporation.

Education
Basic Research
Clinical Research
Clinical Care



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Toxoplasmosis Research
Institute and Center

Chicago, IL
info@toxoplasmosis.org