MSU Moorhead
Department of  Chemistry

Joseph Provost Ph.D.
Biochemistry and Molecular Biology
provost

Lab -208 Science Lab
Office - 407K Hagen Hall
1104 7th Ave. South
Moorhead, MN 56563
Phone (218) 477-5085 / 477-4323
FAX  (218) 477-2018
provost@mnstate.edu

Cell signalling is my bag
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Summer Hockey 2012
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Research / Protocols / CV


The best way to get hold of me is to set up an appointment usually by e-mail.



Lab Rat!
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Research
Many different hormones alter the way a cell can regulate the pH inside of a cell. The Provost and Wallert laboratories collaborate to investigate how several hormones act on lung cells to regulate  signaling molecules and control intracellular pH. 

For each credit of research we require that students work 1 to 2 days a week for 3 to 4 hours for the first semester.  The  time commitment after that increases depending on your project.

biotech research G-Proteins are the first intracellular that tell the cell what to do. Much of the work of our research centers around G proteins, protein kinases, phospholipases and the Na+/H+ Exchanger (NHE). 

Joseph Provost is a Biochemistist and Molecular Biologist in his 16th year at MSUM . Over the past 16 yeas, he has served chair of the Biochemistry and Biotechnology Programmatic Committee at Minnesota State University Moorhead for two years.  He received his Bachelor’s degree in Chemistry from Bemidji State University and his doctorate in Biochemistry and Molecular Biology from University of North Dakota School of Medicine. Dr. Provost did his post-doctoral work as a Howard Hughes Medical Institute Research Associate in the laboratory of Dr. John Exton at Vanderbilt University in the department of Molecular Physiology and Biophysics.

While teaching 12 contact hours (four classes) a semester, advising students and being involved throughout campus and the community on many committees, Dr. Provost has maintained a successful research program where he has been funded with over $3,000,000 in awards from the Autism Foundation, the National Science Foundation, the National Institutes of Health, the State of Minnesota and private foundations.

For the past 16 years Provost was worked with Mark Wallert in the Biosciences department to focus on how G protein coupled signaling pathways cross-talk to signal to growth factor cascades.  These signaling pathways in turn regulate the activity of the Sodium Hydrogen Exchanger (NHE). While NHE regulation is important for intracellular pH homeostasis, a second role for the transporter has also recently gained prominence.

The National Cancer Institute reports that in 2007 there were 213,380 new cases of lung cancer and 160,390 deaths due to both non-small lung cancer (NSCLC) and small cell cancer.  Over 80% of primary lung cancers are NSCLC and while there are a number of clinical trials focused on this disease, there remains less than a 10%, five-year survival rate for patients with NSCLC. Tumor invasion and metastasis are the major causes of mortality in cancer patients.  Cancer cell motility is a complex series of events, which includes the coordination of proteases and cytoskeletal proteins at the leading edge of the tumor. Urokinase plasminogen activator (uPA) and its receptor are directly associated with a poor prognosis in NSCLC. The sodium hydrogen exchanger isoform 1 (NHE) is one protein, which, in the past few years, has gained prominence in the coordination of these events. The NHE exchangers are a family of antiporters which transports an intracellular proton for an extracellular sodium ion resulting in intracellular alkalinization and extracellular acidification. The role of NHE as a focal point for cell migration and regulation of extracellular pH is a newer concept that is vital to understand the mechanism of cell motility.  NHE has two critical functions that are implied in this process 1) coordination of cytoskeletal proteins and signaling complexes and 2) acidification of the extracellular environment. 

Our research focuses on both aspect of NHE.  First is the signal transduction biochemistry involved in regulating the exchanger. We find that the small GTPase RhoA kinase, ROCK is at least partially responsible for the activation of NHE.  Cell growth, invasion and migration of cultured lung cells are all inhibited when either RhoA Kinase or the lipase are inhibited.  We are now working to determine the mechanism by which ROCK drives these events.  Our second focus of study is to determine the relationship between NHE, and urokinase plasminogen activator (uPA) in driving cellular invasion and metastasis. The survival rates for all cancer patients with elevated uPA have a 2/3rd lower favorable prognosis that those patients with low uPA plasma levels.  A study of patients with NSCLC found elevated levels of plasma MMP-9 and uPA as compared to control subjects; they also found that these levels were even higher in those patients with NSCLC metastasis. We used both uPA and the inactive-receptor binding amino terminal fragment of uPA (ATF) to stimulate human lung H460 carcinoma cells.

The long-term goal of our work is to demonstrate that NHE requires Rock phosphorylation and that the phosphorylation coordinates important cytoskeletal binding events driving cell motility.  Furthermore, we hope to find that NHE inhibitors will provide a potential new method to treat NSCLC when used in combination with the current NSCLC inhibitors.  What makes this attractive is NHE inhibitors are already approved for human use and have been used in combination therapies for other diseases with success.  This work is funded by NIH-1-R15-CA135616-01 & NSF-MCB-0817784.


Dr. Provost has been an active member of Project Kaleidoscope's Faculty for the 21st Century and is a Councilor in the Chemistry Division of the Council on Undergraduate Research (CUR).  In the past few years he helped facilitated many workshops throughout the country on teaching investigative laboratories and incorporating research into the undergraduate curriculum as well as give workshops on how to conduct undergraduate research.  Dr Provost has served on the board of directors for the Minnesota Academy of Science and organized several meetings for Tri Beta and MN Acadamy of Sciences. 


Dr. Provost served the Chair of the Undergraduate Affiliates Network (UAN) of the American Society of Biochemistry and Molecular Biology (ASBMB) for five years where he worked on the committee to create a program for universities around the country to accredit their biochemistry and molecular biology degrees/majors.  Dr. Provost is a member of the ASBMB Education and Professional Development Committee. In these positions Provost is responsible for the coordination of resources for biochemistry and molecular biology courses in the nation. For the past six years, Provost has been one of the organizers for the undergraduate poster session and runs one of the sessions at the national ASBMB meeting. Dr Provost is on the editorial board for several journals including Chemical Biology & Drug Design, Biochemistry and Molecular Biology Education (BAMBED) and is a  member reviewing research and teaching grants at the National Science Foundation as well as the National Institutes of Health.

Click here for Information on the 2011 ASBMB UAN & ACS Regional Meeting!

ASBMB Meeting 07
 
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