This is a student drawing of NHE binding ERM and stress fibers while exchanging H+ and Na+

Research is a mixture of hard work, investigation, intellect, frustration and just plain fun.  This is pretty much the principle that we live by in our research laboratory.  Research in our lab is as much about teaching as it is creating new knowledge.  We invite you to consider being involved in research it is a rewarding experience that will impact your life. In the lab we have a number of research projects.  Right now we are working on learning how cells coordinate to control cell movement, migration and when things go haywire, invade and metastasize.  Specifically we work on understanding how three different hormones/agonsists, phenylephrine, LPA and urokinase plasminogen activator act to regulate ERK,, PLD, NHE, stress fiber formation and MMP9.  There are also projects on Malate Dehydrogenase, DNA purification and the biochemistry of autism.

Agonists (or hormones) that signal through hetertrimeric GTP binding proteins are typicaly involved with physiological / biochemical responses such as heart beat, blood pressure, and other short-term effects.  However, some agonists such as lysophosphatidic acid (LPA) binds to receptors that couple to G protiens and instead of changing cAMP or calcium, a growth factor pathway is activated.  We are interested in how LPA and another agonist, phenylephrine (PE) both impinge on the growth factor cascade to activate a map kinase called extra-cellular regulated kinase (ERK).  More importantly we want to learn how this ultimatly leads to NHE activation.

To accomplish these goals, we study cultured lung fibroblasts,  and several human cancer cell lines: lung, ovary and breast cells. The students in the lab use several inhibitors of important proteins and then look for changes in either the regulatory proteins or the exchanger itself.  We also use several normal and mutated clones (proteins), which are often oncogenes to understand the process of cancer.

Some of these protein include the alpha subunit of G proteins, Ras, RhoA, protein kinase C, mitogen activated protein kinase (MAPK also known as extracellular responsive kinase [Erk] also known as p44, p42 protein kinase and a few more things-  (don't ask why, I don't make these things up) heterotrimeric G proteins and phospholipase D.

The list of techniques the students use to discover how these processes grows every day.  In the lab students learn how to culture cells, run western blots, purify and mutate DNA, use a microscope to see GFP fusion proteins (as seen to the left) and to look for stress fibers.  Students also learn how to purify proteins and assay both the exchanger and other enzymes.

So far things look pretty interesting.  Last year the students presented thier work at the MN Academy of Science and Jessica Johnson and Rachel Sang were just two of the several MSUM students awared for best presentation at the Beta Beta Beta poster competition.  In 2006, Rachel won the top honor for the best presentation on her work with PLD.  They are the sixth such students to do so for the last seven years from our lab!  Last year we also went to San Fransisco to present at the national meeting of the American Society of Cell Biology.  In the past few years our students have presented at the American Society for Biochemistry and Molecular Biology in Boston, San Diego, San Fransisco, New Orleans, and Orlando.  This year three students will be presenting at the ASBMB in Washington DC.

ERK bound to Mg+2

Autism is a pervasive developmental disorder with several cardinal features including sensory disturbances, obsessive-compulsive-like behavior, lack of bonding to caregivers and motor disturbances.  This disorder is not as rare as was once previously believed.  Recent epidemiological studies show that autism spectrum disorders now affect 62-67 per 10,000 births.
Research Students with Nobel Prize Lauriat, Ed Fisher	Even though there has been a steady increase in the occurrence of autism, there still is not very much research being conducted to find a biological cause(s) of the disorder.  Most of the research that has been done so far has been genetic linkage studies.  At least one genetic mutation has been identified, Tuberous Sclerosis Complex (TSC) 1 and 2.  Mutation in either of these two genes is characterized by seizures, mental retardation, autism, and tumors. In addition to TSC1 and TSC2 there are also significant changes in several neurotransmitters that lead to the activation of Mitogen Activated Protein Kinase (MAPK also known as ERK) and the small GTP binding protein RhoA in cells. MAPK pathways promote cellular proliferation by activating critical steps in intracellular transduction of survival signals and have a profound effect on the pathology of diseases.
RhoA is a small G-protein that plays a significant role in directing the cytoskeleton of the cell.  In most people with autism have elevated levels of serotonin and lower levels of oxytocin, and vasopressin.  Serotonin is known to play an active role in brain development and may lead to behavioral and brain changes in autistic children. Lower levels of oxytocin and vasopressin, may also play an important role in understanding the cause of autism because these neuropeptide hormones may mediate the rewarding nature of

Lisa Streitz- Lisa (or Sister Streitz from Minot ND) has picked up three majors and has worked on many different research projects including a summer in our lab and another summer working at Harvard.  We are glad to have her work in the laboratory for the past few years.  Right now she is working to purify the very difficult carboxy terminus of NHE.  Then Lisa will be looking to find how and if RhoA Kinase phosphorylates the protein.
	Jennifer Taves - Jennifer is from Wadena MN and is a powerhouse in the lab.  Jennifer has signal handedly moved the focus of the research group to include proteases.  As one of the leaders of the group she is always there to take on a new project or expand a research project.  (Don't roll your eyes on me now Jenn; Provost always has just one more experiment).  Jenn is looking at the relationship between MMP9 and NHE.  Her current project is to see how tumor cells  stop growing with NHE and MMP9 inhibitors in mice!
Dani Rastedt - Dani is one of our Perham MN kids.  Believe it or not, even though she is a Sophomore, she has been working in the lab for over four years!  Dani is our radiation expert working on labeling cells with H-3 lipid and conducting PLD assays.  She is a wonderful young woman that is a real asset to the lab.  Always there with a nice smile, great attitude and strong skills.

Blake Heinz - The man, the myth, the legend, from South Dakota.  This is a kind young man who is involved in everything on campus: research, soccer, CAB, church...  You name it he is involved.  Looking for a good philisophical discussion - he is your man.  Blake is looking at how the PLD isozymes are involved in stress fiber formation, migration and now is working on human lung cancer cell assays with PE, PLA and UPA.  Ask Blake about blots, he loves blots.

Jenny Canine- Jenny is from Forest Lake Mn, is a hardworking and fun person to have in the lab.  She is an RA and one of the leaders of the PreMed Health Professions Club.  Don't know how she does it but she has time to do the research work in the dark (Microscope work) and keep the lab cleanwith some of the others help.  Jenny has won a ASBMB UAN travel award for her work on learning how stress fibers are involved in cell migration at the leading edge of a wound.  Hey Jenny - get back in the dark and  count those cells

Moses Wananu - Moses is from Kenya and is a treat to talk to and work with on a reseach project.  Moses started new frontier in our lab.  He and Jill S. patiently worked on a new project that focused on Autism.  There is very little known about the disorder and so their work used cells from autsistic patients and non-autistic individuals.   Now Moses is working on pruifying and phosphorylating the C-Terminus of NHE. Ask Moses about centrifugation and running!

Craig Kutz-  Craig has been in the lab for two years now even though it is against our policy to have Packer Backers in the lab.  Craig had an amaizing game last year and should be the starting QB this year, but that is just Dr. P and W's opinion... of course that should be enough.  Craig is working on a screen of ERK and MMP9 activation in 5 different human lung cell lines.
	Jason Tan - Jason is from Woodberry (and a few other places), and has been in the lab for just a semester and a half. Jason has already grown a tremendous amount.  Jason worked very hard for a long time to get a spot in the lab and he has done well with the oportunity.  I see him doing great things in the future.   Jason is working with Craig to look at ERK activation in the human cancer cell lines.
Kristopher Kunutson - Coming soon
	Jennifer Smith - Coming soon
Robert Reames - Coming Soon

Where's Jennifer?  Dr. Provost Can't seem to find her! 
Too many Jennifer/Jenny/Jenns for his mind to take in!

Past students - Many students have gone through the laboratory and we remember and miss each and every one of them.  I know many of you read this so let me know what your are up to now days and I will add links and update your activities.  A list of students include: Dan Loban,(DAN THIS IS WHAT WAS ON THE PAGE) just finished dental school and is on active duty in the ARMY - way to go lieutenant Dan (I WILL REPLACE IT WITH ...) Is a Dentist in the Army with the 101st Air Assult.  He had to leave his lovely wife Joy and their one-year old behind as he is being deployed.  We are all proud of you. Christy Broadwell is in her residency at UND.  Amy Krider was working at the University of California-San Diego and is now a science teacher in California (boy is she in for it!). Shanna Williams finishing up at the Army Medical School in Bethesda MA.  Matt Baumgartner is working in the biotech industry (R&D Systems)  in Mpls, Isaac Manke finished his doctorate at MIT and is working in industry and Tracie Teig is in optometry school. Damian Holznagal is at parts unknown. Jodi Lamoureux is at dental school at the U of Minnesota! Lisa Hansen is working in town and so is Michelle Hagen. Andy McCoy is in Medical School at UND School of Medicine and Health Sciences, and so is Heidi Boyum.  Justin Voog is getting an MD PhD at USC SD. Nichole Korpi is at the University of Wisconsin (go cheese heads), Sarah Olmshenk is in optometry school. JaDean Anderson is in Chiropractic School,   Other students are now far and abroad and include, Becky Kuehn, Jessi HoddapeJody Ophdal, Patty Evink, Larry Louisiana, Summer Teigtmier, Breanne Stoltze (working at Cargill).  Kris Altman, Cheryl Sick, Brad Moran,and Melanie Funfar.