Jermeen El-Zabet: January Research Spotlight Award Recipient
Posted: Jan. 23, 2019

Title: Analysis of Biological Network: Ailanthus altissima and Protein Homology Network

Abstract: A network is a group of elements connected by links. Networks consist of two components. The first component is the nodes which represent the elements themselves; the second component is the edges which represent the connections between the nodes. Here, we use networks to study dispersal of the plant Ailanthus altissima, an invasive species known commonly as the Tree of Heaven or the stinking ash. It is native to China and it has no natural herbivores in the United States, so it has become invasive. The goal for this project is to look at how this species is spread throughout the U.S. and compare that with network models of U.S. transportation systems on the hypothesis that its seeds are dispersed long distances by automobiles and trains. Raw transportation systems data were from the U.S. Department of Transportation for both railroads and highways. Data were extracted from GIS flat files using a Geographic Information Systems software package, System for Automated Geoscientific Analyses (SAGA-GIS). Estimates of Ailanthus altissima stem density were obtained from the United States Department of Agriculture (USDA) online data bank, Forest Inventory Data Online (FIDO). Perl script was written to extract data and organize it into networks that could be used to test if Ailanthus altissima density is explained by the connectivity of the U.S. counties. In an unrelated project on Protein Homology Networks, we are using this same network-based approach to study the similarities among proteins in the proteasomes of several model organisms.

Personal Statement: I chose this research project because it opened the door for me to experience computer-based research. Since I had taken Computer Science courses in high school, I wanted to use what I had learned toward the Biological Sciences field. I started this research project in the summer after my freshman year as an undergraduate student, and I worked on it for another year after graduation. In June of 2015, I co-authored a publication in the PhysicaA Journal. I’ve also conducted field research in China with a group of students as we studied plant-animal interactions in the process of pollination. These different opportunities allowed me to experience research in a wet lab throughout my undergraduate classes, computer-based as I obtained data and wrote codes to extract subsets of data, and field research in China. I am hoping that I can further my research in the area of Protein Homology Networks in a clinical setting. In my last year of research, we looked at the proteome of viruses to study amino acid sequence similarities. I am looking for an opportunity to use this background research to see if any drugs or vaccinations could be developed to combat these viruses.

Patrick O’Connell: December Research Spotlight Award Recipient
Posted: Jan. 14, 2019

Title: SLAMF7 is a critical negative regulator of interferon- ⍺ -mediated CXCL10 production in chronic HIV infection

Abstract: Current advances in combined anti-retroviral therapy (cART) have rendered HIV infection a chronic, manageable disease; however, the problem of persistent immune activation still remains despite treatment. The immune cell receptor SLAMF7 has been shown to be upregulated in diseases characterized by chronic immune activation. Here, we studied the function of the SLAMF7 receptor in immune cells of HIV patients and the impacts of SLAMF7 signaling on peripheral immune activation. We observed increased frequencies of SLAMF7 + PBMCs in HIV+ individuals in a clinical phenotype-dependent manner, with discordant and long-term nonprogressor patients showing elevated SLAMF7 levels, and elite controllers showing levels comparable to healthy controls. We also noted that SLAMF7 was sensitive to IFN ⍺ stimulation; a factor elevated during HIV infection. Further studies revealed SLAMF7 to be a potent inhibitor of the monocyte-derived proinflammatory chemokine CXCL10 (IP-10) and other CXCR3 ligands, except in a subset of HIV+ patients termed SLAMF7 silent (SF7S). Studies utilizing small molecule inhibitors revealed that the mechanism of CXCL10 inhibition is independent of known SLAMF7 binding partners. Furthermore, we determined that SLAMF7 activation on monocytes is able to decrease their susceptibility to HIV-1 infection in vitro via down-regulation of CCR5 and up-regulation of the CCL3L1 chemokine. Finally, we discovered that neutrophils do not express SLAMF7, are CXCL10 + at baseline, are able to secrete CXCL10 in response to IFN ⍺ and LPS, and are non-responsive to SLAMF7 signaling. These findings implicate the SLAMF7 receptor as an important regulator of IFN ⍺ -driven innate immune responses during HIV infection.

Personal Statement: My longterm career goal is to become a physician scientist specializing in the development of novel immuno-therapeutics. In particular, I would like to direct my efforts toward ameliorating suffering in children, both directly through clinical work, and indirectly by bringing new drugs to market. Thus far in my training I have taken the first step along this path by joining the DO-PhD program and selecting a mentor who has already accomplished many of my stated goals. Working under the direction of Dr. Andrea Amalfitano has taught me quite a bit about not only science, but also many of the other regulatory and related complications involved in developing and bring a new therapeutic to market.

Patrick O’Connell presenting at the Michigan Osteopathic Association annual Autumn Convention.

My previous research contributions include solving protein structures which were a part of a high impact publication and uncovering the role that human ERAP1 variants have on immune cell functions. Since coming to MSUCOM my recent achievements include the discovery of a novel regulatory mechanism in monocytes and microglia which I have just published a paper on. We are currently working to set up industry collaborations to begin to identify novel small molecules that can modulate this pathway.

I choose this project because of my interests in immune regulation and therapeutic development. My interests lie in becoming a physician scientist, of which there are little to no Osteopathic physicians currently. In the future I hope to develop, and bring to clinic, novel, immune-modulatory therapeutics that will help patients will various immune-mediated diseases.