Request for Funding

Medical Student Research Fellowship for Summer 2002

Mentor: Linda A. Baker, MD
Department: Urology, Division of Pediatric Urology
Room number: J8.110
Mail Code: 9142
Phone number: 214-648-2278
E-mail: linda.baker@email.swmed.edu
Project title: Role of Insulin-3 as the cause of the undescended testicle

Human subjects IRB approved project number (where applicable): in review

Animal subjects IRB approved project number (where applicable): 0865-99-02-1

Project 1

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)
Basic research and animal-based research
Basic research using clinical patient samples

Brief Description of Project:

Cryptorchidism ('hidden testis') is one of the most common human birth defects, affecting 3 out of every 100 newborn males. During embryonic development, the testicle changes its position from adjacent to the fetal kidney to its final location in the scrotum. A cord-like structure called the gubernaculum aids this testicular movement. Although there are many theories concerning how the testis descends, aberration in one or more molecules may result in testicular maldescent. In a few cases, hormone shots can induce descent. However, surgery is typically required to correct the undescended testicle. Surgery is necessary to diminish the risk of infertility, to monitor for testis cancer, and for cosmetic reasons.
Recently here at UTSW, a hormone known as Insulin-3 (Insl3 - also known as Relaxin-like factor or Leydig Insulin-like hormone) was knocked out in mice. The single phenotypic aberration noted was intraabdominal cryptorchidism due to abnormal gubernaculum formation (Nef, S. and Parada, L.F. Cryptorchidism in mice mutant for Insl3. Nature Genetics 22:295-299, 1999.). In this project, the two main goals are to 1) assess the phenotypes in Insl3 heterozygous mutant mice and 2) participate in screening human patient samples for expression of the Insl3 gene.
This summer project will offer the student the opportunity to participate in scientific research design and interpretation and to apply molecular biological and immunohistochemical techniques using the knock-out mouse model and patient samples. If interested, the student will have the opportunity to perform delicate fetal microsurgery. Lastly, the student will have the opportunity to contribute to the understanding of a very common birth defect, thereby helping many affected children.

Project 2

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)
Basic research and animal-based research

Brief Description of Project:

Hypospadias is one of the most common human birth defects, affecting 3 out of every 1000 newborn males. During embryonic development, the tubularization of the penile urethra is faulty. This results in the urethral meatus being located on the ventral side of the penis in a variable midline position between the scrotum and the tip of the penis. Although hypospadias can be explained in some patients by abnormal androgen stimulation or abnormal androgen metabolism, the cause of hypospadias for the majority of patients is unknown. Currently, the only mode of therapy to correct hypospadias is surgical.
The broad, long-term objectives of this project are to assess the role of several cell guidance molecules in urethral development and in the formation of male hypospadias. Preliminary work with knock-out mice created to study these molecules has revealed hypospadias, suggesting that this group of guidance molecules are important in normal penis development.
This summer project will offer the student the opportunity to participate in scientific research design and interpretation, to apply numerous molecular biological techniques using a drug-induced and a knock-out mouse model and if interested, to perform delicate fetal microsurgery. Lastly, the student will have the opportunity to contribute to the understanding of a very common birth defect, thereby helping many affected children.

Previous Research Activities or Publications with Medical Students:

Mentored 3 Summer Students, Summer 2001
1 - High School
1 - College
1 - Medical Student

Mentored two UTSW medical students in the UTSW Medical Student Research Fellowship, Summer 2000.
At the University of Virginia, mentored two summer research students in molecular biology and immunohistochemistry.

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