Patricia A. DeLeon, Ph.D.

Teaching

  • BISC 105 - Human Heredity and Development
  • BISC 403 - Genetics and Evolutionary Biology
  • BISC 492 - Human Molecular Cytogenetics
  • BISC 693 - Human Molecular Genetics (Syllabus)
  • BISC 693 - Human Molecular Genetics (Schedule)

Research Interests

On the left is seen an infertile transgenic sperm with overexpressed Spam1 located in a cytoplasmic droplet (double arrow) on the tail. On the right a wild type sperm is seen with Spam1 in the normal location on the head (single arrow).

The identification of genes and mechanisms that are involved in sperm dysfunction and male factor infertility/subfertility is the focus of our laboratory. We are interested in candidate or novel genes that play a role in spermatogenesis, epididymal sperm maturation, and fertilization. The latter can be considered as the process by which the genome passes from one generation to the next. Not only is the laboratory interested in the function of the genes and their impact on male germ cell differentiation, but also in their regulation (transcriptional and posttranscriptional). Thus our interest lies in the genetic and molecular mechanisms of spermatogenesis, epididymal function, and the molecular aspects of fertilization.

One class of genes being currently studied is the mammalian hyaluronidases which are abundantly expressed in the testis. There are seven family members of these genes and they are tightly linked in two clusters on different chromosomes. The best studied of these is the Sperm Adhesion Molecule 1 (SPAM1) which is widely conserved, being found in every mammalian species that has been studied to date. SPAM1 encodes a sperm membrane glycosyl phosphatidylinositol- (GPI)-linked protein (SPAM1 or PH-20) which plays multiple essential roles in fertilization. These include cumulus penetration, zona pellucida binding, and hyaluronic acid receptor activity during the signal transduction involved in acrosomal exocytosis. We are interested in determining if all the hyaluronidase genes have unique or overlapping functions, or if they operate as a classical polygenic system.

Current Projects

  • The Role of PMCAs in integrating Ca2+ and Nitric Oxide (NO) Signaling in Sperm
    Plasma membrane Ca2+-ATPases (PMCAs) are a family of 4 ubiquitously expressed Ca2+ efflux pumps. They are transmembrane proteins that are encoded by 4 genes unclustered in the genome. Due to alternative splicing there are ~30 PMCA pumps which are differentially expressed in the tissues. In the testis PMCA4 and PMCA1 are expressed and are found in sperm in the ratio of 9:1. These efflux pumps are also expressed in the epididymal, uterine, and oviductal fluids where they are found in exosomes which are capable of delivering them to sperm amid other molecules in their cargo. Our Lab is studying the mechanism(s) by which these transmembrane proteins are delivered to the sperm membrane via the exosomes, as well as the mechanism by which targeted deletion of Pmca4 in mice leads to loss of sperm motility (asthenozoospermia) and male infertility.
  • Reproductive Exosomes and the Transfer of Fertility-Modulating Proteins to Sperm during Their Maturation - Our lab was the first to discover the expression of SPAM1 in the extratesticular pathway (the efferent duct, the epididymis and the vas deferens) as well as the female tract. We have shown that SPAM1 and other GPI-linked proteins are secreted in the reproductive luminal fluid on membrane vesicles (exosomes or microvesicles) which deliver the proteins to the sperm surface. In investigating the mechanisms underlying exosomal cargo delivery to sperm we have identified two mechanisms for the delivery of GPI-linked proteins which are found in a soluble form as well as the membrane–bound form. Delivery from the soluble form is dependent on lipid carriers secreted in the luminal fluid. Currently, we are working on the mechanism of delivery of transmembrane proteins such as Plasma membrane Ca2+ ATPases (PMCAs) which have been discovered solely on exosomes in the biofluids of both the male and female where they are differentially expressed during estrus.
  • The Role of JAM-A in Ca2+ Clearance in Sperm - Another sperm membrane protein in which our lab is interested is Junctional Adhesion Molecule A (JAM-A) which is known to regulate tight junction integrity, and is present between the Sertoli cells that maintain the blood testis barrier. Our lab discovered its presence in human and mouse sperm and showed that its absence results in elevated Ca2+ levels, decreased ATP levels, and reduced sperm motility. Further, we have shown that JAM-A interacts with the Ca2+ extrusion pump (PMCA4) and Ca2+ serine kinase (CASK). Studies are proposed to document this interaction and determine how deletion of Cask might affect the tripartite protein complex, the function of the pump, and sperm motility.

Research Group

  • Amal Aldossary, M.A.
  • Rachel Andrews, B.A.
  • Kathie Wu - Undergraduate researcher.
  • Rebecca Pollak - Undergraduate researcher.
  • Kristine Olli, B.A.
  • Lauren Coffua, B.A.
  • Pradeepthi Bathala, B.A.

Selected Publications

Trustees Distinguished Professor
U.S. Presidential Awardee (PAESMEM)
Faculty Representative to the Board of Trustees

Phone: (302) 831-2249

Fax: (302) 831-2281

Email: pdeleon@udel.edu

Office: 219 McKinly Lab

Lab: 265/267 McKinly Lab

Address:
Department of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

Education

  • B.Sc. (Hons.), M.Sc. - University of the West Indies (Jamaica)
  • Ph.D. - University of Western Ontario (Canada)
  • Postdoctoral - McGill University (Canada)