Medical Student Research Fellowship for Summer 2003
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
Two Projects
Project 1 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 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.). Recently, the receptor for this hormone
(LGR8) was discovered. In this project, the two main goals are to 1) assess
the phenotypes and receptor expression pattern in Insl3 mutant mice and 2) participate
in screening human patient samples for mutations of the Insl3 or LGR8 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 title: Understanding hypospadias at the molecular level
Human subjects IRB approved project number (where applicable):
Animal subjects IRB approved project number (where applicable): 0865-99-02-1
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
Brief Description of Project:
Hypospadias is one of the most common human birth defects, affecting 1 out
of every 125 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:
1. Mentored one UTSW Medical Student, Summer 2002.
Publication as abstract.
1. Sozubir, S., Verma, S., Lonergan, D., Lorenzo, A.J., Nef, S., and Baker,
L.A. Abnormalities of vas deferens in Insulin-3 gene mutant mice: A potential
predisposing factor for testicular torsion. American Academy of Pediatrics Section
of Urology Meeting, Poster #13, October, 20, 2002.
Manuscript in progress for publication.
2. Mentored 3 Summer Students, Summer 2001. (1 - High School, 1 - College, 1 - UTSW Medical Student)
3. Mentored two UTSW medical students in the UTSW Medical Student Research Fellowship, Summer 2000.
4. At the University of Virginia, mentored two summer research students in
molecular biology and immunohistochemistry.
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