The Combined Effects of Dietary Supplementation and Drug Treatment on Colon Cancer Cell Proliferation

Eric Bankaitis

Research Advisor:  Dr. David Threadgill

Research Mentor:  Ms. Erica Rinella

Departmental Sponsor:  Dr. Lillie Searles

Investigations into the chemotherapeutic and chemopreventative properties of various dietary supplements continue as a focus in the field of cancer research. Certain dietary components evidently provide a means to more efficiently treat cancer development and progression in humans. The goal of my research is to test whether treating two human colon cancer cell lines with a Growth Factor Receptor inhibitor in combination with a folic acid, selenium, or calcium supplement, can affect cell proliferation. I hypothesize that if dietary supplementation significantly reduces cancer cell proliferation, then supplementation and drug treatment will combine to further inhibit proliferation. It is also possible that a higher concentration of the test supplements will interfere or enhance the synthetic inhibitor’s activity, so a secondary aim of my project is to investigate this matter.

Steps to uncovering the molecular basis of human pathological angiogenesis: The characterization of RICH2/TEM28

Rachel Currin

Research Advisor:  Dr. Channing Der

Research Mentor:  Dr. Natalia Mitin and Dr. Kent Rossman

Departmental Sponsor:  Dr. Ann Matthysse

The Ras superfamily is a protein family that is mutated in 30% of all human cancers.  Rho-family GTPases are a subset of the Ras superfamily and are involved in cell motility and cytoskeletal organization.  A novel protein called RICH2 (a.k.a. TEM28) has been identified as a regulator of the Rho-family.  Characterized as a GTPase activating protein (a GAP), RICH2 works to effectively inactivate Rho-family GTPases.  RICH2 has also been characterized as a tumor endothelial marker (a TEM).  These proteins are expressed differentially in cancerous tissue and healthy tissue.  In the case of RICH2 (TEM28), expression occurs in the endothelial cells of non-quiescent blood vessels surrounding cancerous colorectal tissue.  It is reasonable to suggest that RICH2 is therefore involved in angiogenesis, the process by which tumors induce capillary growth to obtain required nutrients and allow for tumor expansion.  Anti-angiogenesis drugs have proven effective against some cancers.  Once characterized, RICH2 may become a target for even more effective directed therapies against human cancers.

I have begun to characterize RICH2 by looking at its localization, GAP activity, and GTPase specificity in mammalian cell lines.  I will continue by looking at how elevated levels of RICH2 affect proliferation and migration of endothelial cells as well as angiogenesis.

Experiments in the Role of Inflammation on Norepinephrine Reactivity in Mouse Dorsal Root Ganglion Neurons

Lindsay Erin Rhodes

Research Advisor:  Edward R. Perl, MD

Departmental Sponsor:  Dr. Edward D. Salmon

The dorsal root ganglia of the spinal cord contain the cell bodies of sensory neurons that project from the periphery.  Injury is known to induce physiological changes in the composition of the cellular membrane and connectivity of these sensory neurons.  Nerve growth factor (NGF) can enhance growth and reactivity of cultured dorsal root ganglion (DRG) neurons and interleukin-1B (IL-1B), a pro-inflammatory cytokine, can induce hyperalgesia, hypersensitivity to painful sensations.  Additionally Norepinephrine (NE), a naturally circulating neurotransmitter, is believed to signal neurons through a G-coupled protein pathway; therefore its signal transduction may vary due to small changes in the presence of G-protein subunits in the cellular membrane.  We propose that the presence of IL-1B and NGF during culture alters the physiological responses of DRG neurons to various naturally occurring endogenous and foreign exogenous compounds.  In order to examine these changes further, we will culture DRG neurons from uninjured Prp-GFP transgenic mice (containing a prion promoter and green fluorescent protein (GFP) coding sequence) in the presence of IL-1B and/or NGF and document their responses by whole-cell recordings.  Using a gravity-driven perfusion system, both endogenous and exogenous agents such as NE and Clonidine, will be delivered and responses will be contrasted with control data.  The sensory organ of the skin contains a multitude of different pain sensing terminals ranging from polymodal (C-fiber) to mechanical (Aβδ-, Aδ- and C-fibers).  By observing the morphological characteristics of the DRG cell bodies and testing for physiological characteristics (resting membrane potential, current transduction, chemical sensitivity) in vitro, conclusions can be drawn about the function of the areas they innervate.