University of Chicago Chicago

$62,755

Michael A. Weiss, MD, PhD, Professor Departments of Biochemistry & Molecular Biology 920 E. 58th Street Chicago, IL 60637 Intersex Abnormalities of the Newborn: 3D-NMR Studies To reveal details of how the protein called TDF (testis-determining factor) acts upon genes involved in embryonic sexual development, such as the gene encoding MIS (Mullerian inhibiting substance), which in male embryos reverses the anatomically female development with which embryos of both sexes normally begin. Different mutations in the gene encoding TDF cause various abnormalities of sexual development, often with serious psychosocial impact on affected individuals and their parents. Clarification of how such mutations produce their effects may lead to better means of treatment or prevention of these birth defects. Of particular interest is a mutant TDF that bends DNA differently from normal TDF, and so may exemplify a previously unknown mechansim of gene regulation based on DNA bending.

Basil O'Connor Starter Scholar Research Award

Northwestern University Evanston

$40,000

Amy Bejsovec, PhD, Assistant Professor Department of Biochemistry & Molecular & Cell Biology 2153 Sheridan Road Evanston, IL 60208-3500 Cell-Cell Communication During Drosophila Development To learn how different mutations of the gene encoding a protein called Wg (for its role in wing formation) in fruitflies cause different patterns of embryo maldevelopment. Wg is produced in certain embryonic cells and induces other cells to take specialized form and function. A closely related cell-signaling protein in vertebrates, called Wnt-1, is active at different times in many different embryonic tissues, and certain mutations of the gene that encodes it cause major maldevelopment of the vertebrate embryonic body and disrupt formation of the brain and spinal cord. Detailed knowledge of how Wg works is needed as a basis for learning how Wnt-1 and other related proteins act during early human development, and how genetic or environmental disturbances of Wnt-1 function may cause birth defects whose origins are now unknown.

University of Illinois at Chicago Chicago

$40,000

Alisa L. Katzen, PhD, Assistant Professor Department of Genetics University of Illinois at Chicago College of Medicine 900 S. Ashland Avenue, M/C 669 Chicago, IL 60607-7170 Study of Cell Division Defects During Development To shed light on the likely embryonic development role played by genes of the class called myb, originally identified because some of their mutations are involved in the runaway cell multiplication of various cancers, and later known to be active in the normal cycle of cell multiplication. The myb genes encode proteins that attach to specific segments of DNA and thereby control activity of other genes, seemingly involved in a specific stage of the cell cycle. Rigid positive and negative control of cell cycling is obviously essential to normal embryo development, and genetic or environmental disturbances of such control are presumptive causes of birth defects whose origins are now unclear of unknown.

University of Illinois at Chicago Chicago

$40,000

Benjamin Glick, PhD, Assistant Professor Department of Molecular Genetics & Cell Biology 920 E. 58th Street Chicago, IL 606637 Molecular Analysis of the Organization of the Golgi Apparatus To learn how the Golgi bodies of a cell normally form and take positions around the nucleus. Golgi bodies are unified systems of compartments and conduits in which a wide variety of proteins newly produced by a cell nucleus are chemically tagged, sorted and dispatched to their proper destinations within the cell or at its surface. Much remains to be learned about how these complex organelles work. Many different genetic or external factors may interfere in various ways with their form and function, but are unlikely to be identified until the normal Golgi apparatus is better understood. Golgi abnormalities have been implicated in conditions as varied as autosomal dominant polycystic kidney disease, congenital storage pool disease of platelets, Tangier disease, and congenital dyserythropoietic anemia type II.

University of Illinois at Urbana-Champaign Urbana

$40,000

Cheng-Ming Chiang, PhD, Assistant Professor Department of Biochemistry, 419 RAL 600 South Mathews Avenue Urbana, IL 61801 Role of Cellular Cofactors in HPV Transcription To investigate the mechanism whereby infected cells replicate human papillomaviruses (HPVs), whose effects include genital warts and cancer, as a step toward devising a way to block viral replication and transmission from infected mothers to their babies during birth. HPV infection of an infant's larynx can cause warts that threaten life by blocking breathing. After surgical removal they often grow back, requiring repeated operations over many years.

University of Chicago Chicago

$40,000

Clifton W. Ragsdale, Jr., PhD, Assistant Professor Department of Pharm. & Physiological Sciences 947 E. 58th Street Chicago, IL 60637 Neuronal Patterning in Midbrain Development To chart normal and abnormal formation of the brainstem region called the midbrain, which is centrally involved in control of body movements. Genetic abnormalities and external disturbances of its development may be responsible for some forms of cerebral palsy and hydrocephalus.

Clinical Research

Evanston Hospital Evanston

$48,868

Michael S. Caplan, MD, Assistant Professor Department of Pediatrics 2650 Ridge Avenue Evanston, IL 60201 Pathogenesis of Experimental Necrotizing Enterocolitis To uncover the cause of a poorly understood, life-threatening intestinal disease called necrotizing enteroocolitis, that strikes approximately 10 percent of preterm infants. Affected babies suffer damage to the bowel wall that leads to abdominal swelling, and sometimes perforation of the bowel and severe bleeding. Up to 30 percent of affected babies die and 25 percent of survivors are left with severe, chronic intestinal problems. The researchers will examine the role of certain immune system proteins (platelet activating factor and tumor necrosis factor) that play a role in triggering inflammaion of tissue, and based on what they learn, attempt to devise treatments that can prevent or treat this disease.

Loyola University Medical Center Chicago

$72,000

Patricia L. Collins, MD, PhD Associate Professor Department. of Obstetrics & Gynecology Regulation of Uterine Calcium L-Channel Through Gestation To determine how a recently discovered substance (fetal membrane inhibitor) produced by the outer membrane surrounding the fetus may help prevent preterm uterine contractions. Fetal membrane inhibitor might be useful to prevent or halt preterm labor, but more needs to be known about how this substance works before it can be used therapeutically or can help in devising other new means of treatment. About 10 percent of all babies in this country are born prematurely (beforme 37 weeks' gestation). These babies account for 75 percent of newborn deaths that are not caused by birth defects. Current treatments aimed at preventing or stopping preterm labor are often unsuccessful.

Children's Memorial Hospital Chicago

$58,704

Amy Paller, MD, Associate Professor Department of Pediatrics & Dermatology Children's Memorial Hospital 2300 Children's Hospital Chicago, IL 60614 Correction of Keratin Filament Abnoramlities in Epidermolysis Bullosa Simplex by Normal Keratin Gene Transfer To explore feasibility of gene therapy to correct the skin fragility that characterizes epidermolysis bullosa simplex (EPS), a group of hereditary blistering diseases of the skin and mucous membranes (including the mouth and throat), in which blisters can result from the slightest trauma. In its most severs form, EBS can result in newborn death. But most affected individuals survive with lifelong painful blistering, and in some forms, with scarring, disfigurement, and deformities. This study could also lead to improved treatment of related skin disorders such as bullous congenital ichthyosiform erythroderma and pachyonchia congenita.

Children's Memorial Hospital Chicago

$56,540

Amy Paller, MD, Associate Professor Department of Pediatrics & Dermatology Children's Memorial Hospital 2300 Children's Hospital Chicago, IL 60614 Treatment of Life-Threatening Hemangiomas by Gene Therapy with Anti-Angiogenic Factors To determine whether gene therapy can effectively shrink potentially life-threatening, but non-cancerous, blood vessel tumors of infancy called hemangiomas. Up to 12 percent of infants develop these strawberry-colored "birth marks," most of which are small and disappear by age 10 without treatment. But some such lesiions are large and persist, causing serious complications such as vision loss, airway obstruction, and Kasabach-Merritt syndrome (life-threatening bleeding and heart failure). This study could lead to improved treatment for severe hemangiomas and has broader remifications for the treatment of cancers involving the blood vessels, and possibly for cancer in general.