Degree: Third year Ph.D. student.

Advisor: Dr. Greg Pari

Project Title: Lytic Replication of HHV8.

Project Description:
Our lab studies viral replication of human herpesviruses.  I study HHV-8, also known as Kaposi’s sarcoma associated herpesvirus.  More specifically I am looking at the cis elements and the trans acting factors that are essential for lytic replication. Two of these trans acting factors include PAF (primase associated factor) and orf 50. Orf 50 has the ability to activate the complete complement of lytic genes in HHV-8.  This research is carried out in B lymphocytes and human microvascular endothelial cells were the virus is primarily latent.  Therefore, these cells must be treated with chemicals to induce the lytic phase.

Reasons for choosing UNR CMB program: I came to UNR because I love this area and the school has a wonderful molecular biology program.

Degree: Third year Ph.D. student.

Advisor: William T. Gerthoffer, Ph.D., Dept. of Pharmacology

Project Title:  Effects of HSP27 on p38 MAP kinase-mediated gene expression in bronchial smooth muscle cells.

Project Description:
Our lab studies the p38 mitogen activated protein kinase (MAPK) pathway, which is an intercellular signaling pathway involved in the inflammatory response.  This pathway has been linked to changes in gene expression in airway smooth muscle cells, inducing them to produce proinflammatory proteins such as cytokines and chemokines, which may play a role in such airway diseases as asthma, COPD, and ARDS.  My project focuses on a small heat shock protein 27 (HSP27), and its role in p38-mediated gene expression changes.  HSP27, an actin-capping protein, has been shown to be a downstream substrate for the p38 MAPK pathway.  Upon phosphorylation, it is released from the actin, allowing for actin polymerization and cytoskeletal remodeling.  It is our belief that through its modulation of cytoskeletal activity, HSP27 may be affecting p38 MAP kinase-mediated gene expression through an outside-in signaling mechanism.  Elucidation of this pathway may lead to a better understanding of the mechanisms of airway inflammation, and offer possible targets for the treatment of such disorders.

Advisor: Dr. Stephen St. Jeor

Degree: Senior Graduate Student, Ph. D. Program

Project Title: Generation and characterization of  neutrazlizing antibodies against Sin Nombre and Andes hantaviruses.

Project Description:
Our lab is interested in identifying common neutralizing epitopes of South (Andes) and North American (Sin Nombre)  hantaviruses to determine their potential for vaccine use. Based on the examination of patients infected with these viruses, those that make high titered antibody early in infection recover more rapidly than those that fail to produce high levels of antibody.   To achieve this goal we have used the following approaches:  1) A comparison of the neutralizing ability of convalescent sera from patients infected with either North or South American viruses reveals that their sera neutralizes the homologous virus to a much greater extent than the heterologous virus.  However, there appear to be shared epitopes between both North and South American hantaviruses based on this data. 2) We have isolated human recombinant fab molecules from a phage display library prepared from the bone marrow of convalescent patients previously infected with hantavirus. The fabs were isolated using intact virus and  tested by both fluorescent antibody and virus neutralization to determine their  ability to react with North and South American viruses.  To date, one fab against Sin Nombre virus has shown an ability to partially neutralize the virus.  Neutralization ability was tested with both infectivity and plaque neutralization assays.  The complete antibody of this fab was produced and tested for neutralization and cross-reactivity. The whole antibody (IgG) cross-reacted with Andes, Sin Nombre (condsidered New World hantaviruses )and the Old World hantavirus prototype, Hantaan virus.  Further characterization of this antibody showed that it was specific against the virus glycoprotein G1 but did not neutralize more efficiently at higher antibody concentrations.  Future goals are to produce and test additional fabs for neutralization. 

Reasons for choosing UNR CMB program: The CMB program here at the University of Nevada, Reno is excellent.  We have many excellent researchers who are well known in their respective fields.  The campus is very nice and the surrounding area (Lake Tahoe, etc.) gives one ample opportunity for outdoor activities.  Reno has an international airport, which makes it very convenient for friends and family to visit.

Degree: 1st year Ph.D. student.

Advisor: Dr. Greg Pari

Project Title: Characterizing UL84, a Cytomegalovirus protein.

Project Description:
I have worked in Dr. Pari’s Laboratory as a technician for two years and have recently decided to pursue a Ph D in Cell and Molecular Biology.  I am currently working on further characterizing a Cytomegalovirus protein, UL84.  Little is known about the function of UL84 except that it is an early gene that is essential for replication and interacts with the immediate early protein IE2.

Reasons for choosing UNR CMB program: My undergraduate degree was completed at UNR in Biochemistry and I am originally from this area.  I enjoy all of the activities that the Sierra Nevada Mountains offer such as skiing, snowboarding, hiking, fishing, and sailing.  My family is also near by, and has lived in the area for nearly 25 years. 

College/year: Albertson College of Idaho, 1997

Project Title: The role of p21-activated kinases in smooth muscle.

Advisor/Department: William T. Gerthoffer, Ph.D., Dept. of Pharmacology

Project Description:
The Gerthoffer lab is generally interested in the molecular signaling pathways that regulate various physiological processes in smooth muscle, including contraction, migration and gene expression.  One of our major projects involves defining the phenotype and gene expression profile of airway smooth muscle cells under conditions which mimic an inflamed, asthmatic airway.  My research focuses on elucidating the signal transduction pathways of the p21-activated kinases (PAKs) and determining their contribution to cytoskeletal dynamics and gene expression in airway smooth muscle cells under these conditions.  I¹ve developed recombinant adenoviruses encoding wild type, and kinase deficient and constitutively active mutant forms of PAK1, the prototype isoform.  By using the viral vectors to overexpress these forms of the protein, I¹ve been able to determine that PAK1 signals through a member of the family of mitogen activated protein kinases (MAPKs), p38 MAPK, to help regulate cell migration.  Currently, I¹m using a luciferase reporter construct to determine whether PAK1 plays a role in the expression of cytokine genes by signaling to the transcription factor NFkB.


Publications:
Hedges, J.C., Dechert, M.A., Yamboliev, I.A., Martin, J.L., Hickey, E., Weber, L.A., and W.T. Gerthoffer (1999).  A role for p38MAPK/HSP27 pathway in smooth muscle cell migration. J. Biol. Chem. 274: 24211-24219.

Dechert, M.A., Holder, J.H. and W.T. Gerthoffer.  p21-activated kinase-1 participates in tracheal smooth muscle cell migration by signaling to p38 MAPK.  Am. J. Physiol. Submitted.

Garcia, J.G.N., Liu, F., Verin, A.D., Dechert, M.A., Gerthoffer, W.T., and D. English.  Sphingosine 1-phosphate promotes vascular endothelial cell barrier integrity by Edg receptor-dependent cytoskeletal rearrangement: possible implication for vascular maturation.  J. Clin. Invest. Submitted.

Degree: 2nd year Graduate Student

Advisor: Dr. Stephen St. Jeor, Department of Microbiology

Field of Interest:  Hantaviruses

I came  to the UNR first for an intensive English training. While there  I applied  for a Research  Assistantship in the Cell and Molecular Biology Program.  The program had a number of research opportunities, which I found interesting and matched with I want to do.

My principal goals are to learn as much as possible about Molecular Biology, and to apply this information to my Ph.D. After completing my training I would like to go back to my country and apply what I learned to problems which occur there.

I started my first lab. Rotation in Dr. St Jeor’s Laboratory where I gained experience in Protein purification, cloning and expression of hantavirus glycoproteins.

I plan to continue in the same area for my Ph.D. dissertation, under the  direction of Dr St Jeor, because  I’m interested in what his lab is doing and he is willing to spend the time needed to help me in my research program.

My immediate goal is to produce monoclonal antibodies by fusing  Spleen cells from deer mouse  infected with wild type hantavirus with myeloma cells from Balb/C mice.  Using this approach I hope to isolate hybridomas that produce monoclonal antibodies capable of neutralizing virus infectivity.

Degree: 2nd year Ph.D. student

Advisor: Dr. Kenneth Hunter

Project Description: 
I am interested in the design of genetically engineered tumor cells for use in the development of cancer therapies.  In particular I am interested in the induction of effective immune responses to cancer based on T cell activation.  Transgenic tumor cells engineered to express immunomodulatory molecules such as T cell costimulatory signals are the main focus of my research.

Reason for choosing UNR CMB program: Reno is a great place to live if you like mountain biking, hiking, skiing or a myriad of other outdoor activities. The CMB program is small enough to allow for ample interaction with your fellow students and professors.

Advisor: Dr. Kenneth Hunter.

Project Description: 
The aims of the project I am working on in Dr. Ken  Hunter's lab are twofold: one, to further characterize and understand the molecular elements of autoimmunity that contribute to multiple sclerosis; and two, to develop a novel preventative treatment strategy for MS-susceptible individuals.  I'm currently studying experimental autoimmune encephalomyelitis (in mice), which is the universally accepted animal model for demyelinating diseases such as MS.

Reason for choosing UNR CMB program: I grew up in Reno, but I've also lived in different parts of the country such as Maryland and Southern California.  Hands down, Reno is the best place to live!  Besides the great setting in Reno, I love UNR because it has all the advantages of a big state school but is small enough that you don't feel lost in the crowd.  The CMB program is great because the faculty and staff are very dedicated to student education.  It's also an advantage to the students that there is such a large variety of research taking place here in the biological sciences.

Degree: 1st year Masters student

Advisor: Dr. Stephen St. Jeor, Department of Microbiology

Project Title: Pathogenesis of cytomegalovirus latency in vascular endothelial cells.

Project Description:
My name is Rachel Mantovani and I am an international student from Brazil.  Currently I am a graduate student in the CMB program working on my Master thesis in Dr. Stephen St. Jeor's lab. My project is focused on the pathogenesis of cytomegalovirus latency in vascular endothelial cells. I have just started my project but it promises to be very exiting.

Supervisor: Dr. Esmail Zanjani.

Project Title: Hemoglobin expression in a fetal environment from bone marrow-derived adult human hematopoietic stem cells.

Project Description:
The human hemoglobin (Hb) molecule consists of two duplicate polypeptide chains in combination with four heme groups. The alpha- and beta-globin gene families express the two polypeptides. These loci are activated towards the end of the third week of gestation and coordinately expressed throughout development. However, regulation of each locus present on different chromosomes is independent, as the level of expression of one has no effect on the other. Hb switching occurs as development proceeds from one stage to another.  The Hb types are 1) embryonic: z₂e₂,  a₂e₂ and z₂g₂;  2) fetal: a₂g₂;  and  3) adult: a₂b₂ (>98%, adult major), and a₂d₂ (<2%, adult minor).

Our in-vivo sheep model system was used to determine if the fetal micro-environment would cause the adult stem cells to revert to producing fetal  Hb. This model uses early gestational age sheep fetuses and transplants them with human hematopoietic stem cells (HSC) before the development of the immune system in the sheep. Human HSC persist in the xenograft with multi-lineage expression. Sheep provide a developmental stage specific microenvironment as sheep undergo Hb switching as well.

Degree: First year Ph.D. student

Advisor:  Dr. Stephen St. Jeor

Project Description: 
I'm currently working for Dr. St. Jeor. My project is to make HCMV cDNA library. Once the library is made I'm  going to screen it for latency associated genes.

Reason for choosing UNR CMB program: I came to UNR because the school has a good CMB program and offers to pursue an advanced degree under the advisement of outstanding researches. I also like the area giving lots of opportunities for rock-climbing, hiking and skiing.

Degree: I’m 2^nd year Ph.D. Student. I came to the UNR one year ago and had the honor to rotate in Dr. St. Jeor’s, Dr.Hudig and Dr. Gerthoffer’s labs. Now I study in the lab of Dr. Gerthoffer.

Project Title: Mitogen-activated kinases (MAPKs).

Advisor/Department: William T. Gerthoffer, Ph.D., Dept. of Pharmacology

Project Description:
Our laboratory is doing research in molecular signaling pathways, which are involved in regulation of many fundamental cell processes. We are interested in mitogen-activated kinases (MAPKs) as members of discrete signaling cascades and in effects they could cause in eukaryotic cells. It has been already shown that MAPKs regulate cytokine gene expression in human airway smooth muscles. An understanding of such a mechanism could be useful in examining the causes of numerous pathological states. My project will focus on the role of p38 MAP kinase pathway in stabilization of particular cytokine mRNA transcripts in smooth muscle cells.

Reason for choosing UNR CMB program:
I would like to add a little bit about the UNR program. I like Reno as a calm, sunny town and I like the University of Nevada as a place, which provides good opportunities for international students doing research. It is a big pleasure to communicate with people I met in UNR; especially I’m lucky to have such friendly coworkers.

Hi. My name is Albert Rizvanov. I am an international student from Russia. I’ve got my degree in Microbiology from Kazan State University, Kazan, Russia.

Why did I came to Reno? Well, it wasn’t my choice at that time. I’ve won an undergraduate student exchange scholarship to go to one of the American universities for one year. And they decided to send me to the University of Nevada, Reno. When I came to UNR I had an honor to work in the lab of Dr. Weber. After few months I decided to apply to graduate school. I got accepted to Cell and Molecular Biology program, went back to Russia to defend my thesis, and came back to UNR as a graduate student. Currently I am working in the lab of Dr. St. Jeor. 

I enjoy living in Reno very much. I like almost everything about it. I like dry warm climate, I like scenery, tourist attractions and entertainment in city. It’s not crowded as in big cities, yet there is plenty to do. University itself is OK. It’s not the biggest and most famous university out there, but it’s not the size of the university that matters, it’s people that you are working with.

Now, if you don’t mind, I would like to say a few words about myself. As I said, I am a graduate student at CMB. I guess this is my main hobby. I am also black belt in Shotokan Karate. I consider myself a decent computer technician and one day I plan to pass A+ certification test just for fun. I like sci-fi movies and role-playing games.

Degree: Ph.D. student.

Advisor: William T. Gerthoffer, Ph.D., Dept. of Pharmacology

Project Title:  Characterization of smooth muscle cells located in the G.I. tract.

Project Description:
Sa-Bye-Dee (that means hello in my native language).  My name is Sonemany Salinthone, but I prefer to be called Soom.  I'm originally from Chico where I got my bachelor's (yes, it's a party school, but only to those who look for them).  This is my first year and I'm currently doing my second rotation in Dr. Gerthoffer's lab.  I am trying to characterize smooth muscle cells located in the G.I. tract.  What I will essentially do is stimulate colon cells using various cytokines and see if there is an increase in mRNA expression of several genes: Rantes and MCP-1 among others.  I will then inhibit the expression of these genes using several drugs to determine which regulatory pathways control gene expression.

Contact: ro@physio.unr.edu
Phone: (775) 784-1463
Fax: (775) 784-6903

Education:

Advisor: Dr. Burton Horowitz

Research interests:
My current research focuses on the molecular properties and physiological roles of small conductance Ca ²⁺-activated K⁺ (SK) channels, which are involved in inhibitory neurotransmission in gastrointestinal smooth muscles.

Publications:

Ro S, Horowitz B and Koh SD. Molecular characterization of an α1I T-type calcium channel in mouse colon. In preparation, 2002

Ro S, Koh SD, Perrino BP, Sanders KM and Horrowitz B. Alternatively spliced mSK2 channels regulated by Ca²⁺ -calmodulin protein kinase II. In preparation, 2002

Koh SD, Monaghan K, Ro S, Horowitz B and Sanders KM. Purinergic effects on two types of inward currents in murine colonic myocytes. Submitted, Am J Physiol, 2002

Kim YC, Koh SD, Ro S and Sanders KM. Voltage-dependent inward currents of interstitial cells of Cajal from murine colon and small intestine. Submitted.  J Physiol, 2002  

Koh SD, Monaghan K, Sergeant G, Ro S, Walker RL, Sanders KM, and Horowitz B. TREK-1 regulation by nitric oxide and cGMP dependent protein kinase: an essential role in smooth muscle inhibitory neurotransmission. J Biol Chem 276:44338-44346, 2001

Ro S, Hatton WJ,  Koh SD and Horowitz B. Molecular properties of small conductance Ca²⁺ activated K⁺ channels expressed in murine colonic smooth muscle. Am J Physiol 281: G964-G973, 2001

Koh SD, Monahgn K, Ro S, Mason HS, Kenyon JL and Sanders KM. Novel voltage-dependent non-selective cation conductance in murine colonic myocytes.  J Physiol 533: 341-355, 2001

Advisor: Dr. Greg Pari.   

Degree: I am a 3rd year graduate student in CMB program working on a Ph.D. 

Project Title: Subcellular localization  of HCMV UL84 is influenced by the presence of DNA replication proteins and orilyt.

Project Description:
The UL84 ORF encodes a 65 kDa protein which is required for origin-dependent DNA replication and interacts with IE2 in lytically infected cells.  The exact role, in DNA replication, for UL84 is unknown.  In order to determine if the presence of the identified HCMV replication proteins interact with, and affect the subcellular localization of UL84 in transiently transfected cells, we ligated the UL84 ORF in the same reading frame context as EGFP.  This plasmid, pUL84-EGFP, produces a protein product with EGFP fused in frame with the UL84 ORF.  The correct molecular weight and presence of a fusion protein was confirmed by western blot.  This protein was fully functional in that it complemented origin-dependent DNA replication in the transient replication assay.  Using this construct, we show that UL84 alone is capable of localizing to the nucleus of transfected cells displaying a diffuse staining pattern.  The addition of IE1/IE2 to the transfection mix does not appear to alter the diffuse staining pattern.  The cotransfection of UL70, UL105, UL102, UL54, UL57, UL44, UL112/113, UL36-38 and HCMV oriLyt along with pUL84-EGFP resulted in a punctate nuclear pattern of the EGFP-UL84 fusion protein.  This change in subnuclear compartmentalization of the EGFP-UL84 fusion protein to a more punctate pattern  is observed only when all the replication proteins are expressed in transfected cells along with oriLyt.

Reasons for coming to UNR CMB. I choose UNR for my Ph.D study because Reno is a nice quiet small town for study . There are a lot of fun things to do here and I love the people here: they are wonderful!