|
Home
Letter from the Directors
Reproductive Science at Northwestern
Administration & Faculty
Research Areas
CRS Members, Students, Research Staff, and Support Personnel
Grants
Seminars
Minisymposium
Newsletter
Training Programs for Undergraduate, Graduate, & Post-Docs
Marcia L. Storch Scholarship Fund for Undergrad Women
CRS Go-to-Meeting Travel Award for Undergraduates
Sites of Interest
Support CRS
|
|
|
|
Testis Function
Bartles, J. |
Goldberg, E. | Milad, M. |
Scarpulla, R.
|
James Bartles, Ph.D.
Department of Cell and Molecular Biology
Ph.D., Washington University
|
 |
The plasma membrane is the interface between the cell and the environment; it is a site where
one can find a host of specializations that appear to be remarkably well-tailored to the
needs of the cell. Examples include: plasma membrane domains; diffusion barriers;
projections such as microvilli and stereocilia; invaginations such as coated pits and
caveolae; and junctions of various types. Although these plasma membrane specializations
differ from one another in many respects, they share a common structural organization:
they are sites where elements of the cortical cytoskeleton are linked, directly or
indirectly, to transmembrane proteins of the overlying plasma membrane. The result is to
tether or cluster integral plasma membrane proteins, peripheral membrane proteins and
cytoskeletal proteins at these specific sites and afford paths along which signals can be
relayed between the cell surface and interior. The objective of our research is to
identify and characterize novel membrane and cytoskeletal proteins of plasma membrane
specializations. Much of our recent work has centered on an analysis of the plasma
membrane specializations of the cells of the male reproductive system, in particular the
domains and diffusion barriers present within the plasma membrane overlying the tail of
the mammalian spermatozoon and the intercellular junctions formed between Sertoli cells
and developing spermatids in the seminiferous epithelium.
Recent Publications:
Cesario MM, Bartles JR 1994 Compartmentalization, processing and redistribution of the plasma membrane protein
CE9 on rodent spermatozoa: relationship of the annulus to domain boundaries in the plasma
membrane of the tail. J Cell Sci 107: 561-570.
Cesario MM, Ensrud K, Hamilton DW, Bartles JR 1995 Biogenesis of the posterior-tail plasma membrane domain of
the mammalian spermatozoon: targeting and lateral redistribution of the posterior-tail
domain-specific transmembrane protein CE9 during spermiogenesis. Dev Biol 169:473-486.
Bartles JR 1995 The spermatid plasma membrane comes of age. Trends Cell Biol 5: 400-404.
Bartles JR, Wierda A, Zheng L 1996 Identification and characterization of espin, an actin-binding protein localized to
the F-actin-rich junctional plaques of Sertoli cell ectoplasmic specializations. J Cell Sci 109:1229-1239.
Sekerkova G, Zheng L, Loomis PA, Changyaleket B, Whitlon DS, Mugnaini E, Bartles JR. Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells. J Neurosci. 2004 Jun 9;24(23):5445-56.
Top | Email Me | Dept. Home Page
|
Erwin Goldberg, Ph.D.
Departrment of Biochemistry, Molecular Biology and Cell Biology
Ph.D., State University of Iowa
|
 |
Mammalian spermatogenesis
is a complex process of cellular differentiation, encompassing unique cytological and
molecular changes that culminate in the formation of spermatozoa. We are particularly
interested in enzymes and proteins that appear during mammalian spermatogenesis and are
unique to the spermatozoon. The best-studied example is lactate dehydrogenase (LDH-X;
LDH-C4), which is synthesized in the primary spermatocyte during the midpachytene phase of
the first meiotic division.
To understand the mechanisms regulating this remarkable
time- and cell-specific process, we have cloned and sequenced the promoter region of the ldh-c
gene. We are investigating the roles of both cis- and trans-acting
regulatory elements. Differential methylation of the CpG-rich promoter has been shown to
regulate expression negatively in tissues lacking LDH-C4.
We are also exploiting the restricted cell-type
expression of LDH-C4 to tackle problems in contraception technology and fertility control.
LDH-C4 has been successfully used as an antigen to provoke antibodies against sperm. These
antibodies interact with sperm in the female reproductive tract and effectively block
fertilization. Ongoing work is directed toward developing a contraceptive vaccine using
both synthetic peptides (comprising unique epitopes of the native protein) and recombinant
viruses encoding the human LDH-C gene as potential immunogens. We are identifying and
characterizing additional antigens capable of inducing infertility using sera derived from
infertile patients.
Recent Publications:
Li, S., Zhou, W., Doglio, L. and Goldberg, E. (1998) Transgenic mice demonstrate a
testis-specific promoter for lactate dehydrogenase (LDH). J. Biol. Chem. 273:31191-31194.
Goldberg, E. (1998) Human LDH-C peptide as an immunocontraceptive. In: Proceedings of
the 10th International Congress of Immunology, New Delhi, India, 1-6 November (Eds.
G.P.Talwar, I. Nath, N.K. Ganguly, K.V.S. Rao) Monduzzi Editore, Bologna, Italy, Publ., pp. 1327-1332.
Ambhaikar, M. and Goldberg, E. (1999) DNA-protein interactions in the CCAAT box region
of the murine lactate dehydrogenase C promoter. Molec. Reprod. Devel. 52:360-365
Xue, J.-C., and Goldberg, E. (2000) Identification of a novel testis specific leucine
rich protein. Biol. of Reprod. 62:1278-1284.
Somwaru L, Li S, Doglio L, Goldberg E, Zirkin BR. Heat-induced apoptosis of mouse meiotic cells is suppressed by ectopic expression of testis-specific calpastatin. J Androl. 2004 Jul-Aug;25(4):506-13.
Top | Email Me | Dept. Home Page
|
Magdy P. Milad, M.D.
Department of Obstetrics and Gynecology
M.D., Wayne State University
|  |
My basic science research activities investigates the progesterone receptor located on the
head of spermatozoa. Progesterone induces the acrosome reaction by causing calcium influx presumably at the progesterone receptor.
However, this membrane bound receptor has not been well characterized. Some immunosuppressant drugs have been found to interact with progesterone receptor chaperone proteins and attenuate progesterone mediated transcription in some cell systems. Preliminary results suggest that FK506, an immunosuppressant drug, does induce the sperm acrosome reaction independent of the presence of progesterone. This may have important implications for facilitating in vitro fertilization of human oocytes and may have far reaching implications for contraception.
Stress has long been implicated in adverse pregnancy outcome although the literature in this regard is somewhat lacking. My clinical research involves measuring markers of stress and correlating these results with pregnancy outcome among patients undergoing IVF. This study will quantitate stress levels using biochemical and subjective tests in patients who have achieved pregnancy while undergoing assisted reproduction.
Recent Publications:
Dragisic KG, Milad MP. Sexual functioning and patient expectations of sexual functioning after hysterectomy. Am J Obstet Gynecol. 2004 May;190(5):1416-8.
Grube JO, Milad MP, Damme-Sorenen J. Preemptive analgesia does not reduce pain or improve postoperative functioning. JSLS. 2004 Jan-Mar;8(1):15-8.
Top | Email Me | Dept. Home Page
|
Richard C. Scarpulla, Ph.D.
Department of Cell and Molecular Biology
Ph.D., Albert Einstein College of Medicine
|  |
The capacity for oxidative metabolism is a fundamental property of the differentiated state
that varies widely among animal cells and tissues. Differences in respiratory function in
both normal cells and in a variety of cellular pathologies are reflected in the number,
size, and morphology of mitochondria as well as in the expression of respiratory gene
products. A fundamental issue is how the biosynthetic activities of nuclear and
mitochondrial genetic systems are coordinated to meet cellular energy demands. Because of
the limited coding capacity of the mitochondrial genome, oxidative function relies upon
nuclear genes for the majority of respiratory subunits and all of the gene products
required for the transcription and replication of mitochondrial DNA (mtDNA).
Characterization of mammalian genes encoding the respiratory cytochromes has led to the
discovery of nuclear respiratory factors (NRFs). These nuclear transcriptional activators
promote the expression of genes encoding both respiratory subunits and key components of
the mtDNA transcription and replication machinery. These observations have led to the
hypothesis that NRFs may be the targets of extra- and intracellular signaling pathways. As
such, they would relay regulatory signals to the mitochondria via their activation of
nuclear genes and also communicate the oxidative state of the cytoplasm to the nuclear
transcriptional apparatus. In this way NRFs may serve to integrate nuclear and
mitochondrial genetic systems to accommodate cellular demands for respiratory energy. Our
long term objectives are to further define the molecular interactions and physiological
functions of NRFs and related activators.
Recent Publications
Gleyzer N, Vercauteren K, Scarpulla RC. Control of Mitochondrial Transcription Specificity Factors (TFB1M and TFB2M) by Nuclear Respiratory Factors (NRF-1 and NRF-2) and PGC-1 Family Coactivators. Mol Cell Biol. 2005 Feb;25(4):1354-66.
Cam H, Balciunaite E, Blais A, Spektor A, Scarpulla RC, Young R, Kluger Y, Dynlacht BD. A common set of gene regulatory networks links metabolism and growth inhibition. Mol Cell. 2004 Nov 5;16(3):399-411.
Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. 2004 Feb 15;18(4):357-68.
Top | Email Me | Dept. Home Page
|
|
|
