DR. BRAD STITH, photo of Dr. Stith
UNIVERSITY OF COLORADO DENVER, BIOLOGY
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Contact info, Dr. Stith's CV, campus maps,   ANIMAL CARE FORMS  - IACUC     Email me at: brad.stith@ucdenver.edu


I. Undergraduate Research--    Getting a biology degree without lab research experience is like getting a degree in tennis without ever playing tennis --take a look at this link for detailed information on the value of undergraduate research- click here.  Read an open letter from a student about the value of undergraduate lab involvement (click here)

Over just the last 6 years, these students (among others) used their work in my lab to go on to great careers:            RYAN BATES (now working at Anschutz Medical Campus, Univ CO Denver)

KULAN BATABAYAR (just finished a Ph.D. at A. Einstein in New York, just left for Cambridge England on a PostDoctoral fellowship)

TIMOTHY SILVERSTEIN (now in Ph.D. program at Mount Sinai New York)

THOMAS MORRISON (received Ph.D. at UNC, Chapel Hill, now working in their virus center)

JASON STAFFORD (now in a Ph.D. program at UT SW; four Nobel laureates are on that campus)

WILLIAM HOLLAND (received a BS, MS in our department, Ph.D. at University of Utah, now a PostDoctoral Fellow at UT SW)

JEFFERY TAYLOR JUERGENS (now in a Ph.D. program in Pharmacology at Univ CO Denver -AMC campus)

A national organization, the Council on Undergraduate Research, facilitates undergraduate involvement-- to go to their web site, click here.

WebGURU: An IMPORTANT web site for undergraduate researchers: http://www.webguru.neu.edu/

THE NATURE OF RESEARCH -supporting funding for basic research (versus just "applied" research):  "Barnett Rosenberg wasn't trying to cure cancer...wasn't working on cancer (or)....on any disease-related problem (or)....with human cells. All he was trying to do was to test a hypothesis about what would happen when dividing bacteria were placed in a strong electric field. Yet he may have saved the lives of more cancer patients than most of the cancer researchers in the world put together."  ..."a very important (idea)...is that in science there is no such thing as useless information." Go to this web site: http://www.asbmb.org/Page.aspx?id=1916

                                                                                                                            photo: UCD undergraduate research students at the ASCB meeting in San Francisco, CA

"The normal attitude (of a scientist) is a disquieting sense of being wrong.  The work is open-ended, the results uncertain, and decisions are "curiosity-driven." Lewis Thomas, Physician/Researcher.

"SUCCESS IN SCIENCE GOES ONLY TO THOSE WHO ARE UTTERLY PARANOID ABOUT THINGS GOING WRONG AND UTTERLY OBSESSIVE ABOUT PREVENTING MISHAPS." JMW SLACK.
                                                                        


II.  Presentations and Web Papers (to view the slide presentations, use IE not Netscape Communicator or Adobe PDF reader)

1. Presentations on Undergraduate Research at Clarion University (Oct. 10, 2008), Northern Michigan University (Feb. 1, 2008), and at Southern Connecticut State University (Aug. 23, 2005), showing data on the educational value and tips on achieving a successful program. Click here for PowerPoint slides (requires pdf reader).

5 Funding Sources for Undergraduate Research (presentation at FASEB 2001)

6.  Click here to link to my paper on use of Animation in Teaching Cell Biology (in Cell Biology Education). CLICK HERE FOR TALK

2 GRANT WRITING "HOW TO." Presentation at Council on Undergraduate Research (CUR)  Proposal Writing Conference

7. Adjusting to a PUI after a research institute or med center
                    Response to "Adjusting to a PUI... "

3. FASTLANE and Grants.gov...a "How To"; Presentation given at the CUR Proposal Writing Institute

8. Use of WebCT for a web site for a lecture course
Link to copywrited article on use of WebCT by Dr. Stith

4. Grant Writing Skillswith emphasis in Biology (given at CUR National Conferences 2000, 2002, 2006)
                CUR 2002 PHOTOS

9 Web animation and video in teaching.  Gone are the days of overheads and blackboards!! Here is a presentation on How to Use PowerPoint Animation in lecture; click here


III.  Courses taught by Dr. Stith---From a past student of mine:  "I took you for developmental biology, cell signaling, and advanced cell biology...Well, I am 3 weeks into my first semester of medical school at Ross University and I wanted to tell you how amazing those three classes I took with you were.  I am about 1-3 months ahead of my fellow classmates b/c of those three classes.  It has made my transition into medical school much easier.  I am even having my mom send me all of your lecture CDs you gave us to help me study" (January 2006).  An Oct 2007 email from a student of mine now at UC medical school: "I did get into medical school!!! Today in class, one of our professors asked if anyone knew what Notch was. It was nice to be the only person of 157 people to know what notch was and answer the question. My answer could have been better, but I got the point across!! I'm really glad I took all of your classes!!!  We actually use the same book by Alberts. They just skim the surface of these topics leaving some people lost.  However, I feel very well prepared for this block b/c of your classes!!!"

For a "how to" on searching for scientific articles using PubMed, click here  (pdf Adobe file).  This info is to be used in my courses that require a student presentation on original research papers. 

For instructions on how to develop Oral, Scientific Presentations, click here  and also here

For instructions on how to make a PowerPoint slide for a large poster, click here

How to take Essay Exams (especially important for my upper level courses); click here.

1. Developmental Biology 4054/5054. Once you know your user name and password, Go to the CU Online web page, go to the upper right corner, under "Course Login" and click on Blackboard Login.  To go to the CU Online web page,  click here .  For the course packet: click here.   For due dates, click here.  See these web sites: Jeff Hardin 's Amphibian Embryology Tutorial and Frog embryology.

2. Advanced Cell Biology 4064/5064 Course Packet                                        3. Cell Biology 3611  
4. Cell Biology Laboratory course                                                                     5. Cell Signaling 4550/5550                    6. Math 4027/5027

IV. Use of the popular movie Lorenzo's Oil  in teaching Cell Biology: To view Dr. Stith's explanations of the movie, "click here for info on Lorenzo's Oil."  To see a Myelin Foundation SLIDE SHOW on the MECHANISM Of Lorenzo's Oil, click here. Updated 2008 student talk (click here)FOR RECENT NEWS on Lorenzo's Oil: (1) CLICK HERE           (2)  HERE    (3)  here     and    (4) especially here for an Aug 2005 article supporting the use of Lorenzo's Oil.   See article on Dr. Moser.  To visit the  Myelin Foundation, click here.  (5) Lorenzo passes away May 29 2008 (click here).

V.  Research  Two main areas of our research: 1. Cell Division/Insulin Action and 2. Fertilization.  See this summary;  click hereOUR RECENT PUBLICATION was selected for a "highlight" article by the American Society for Biochemistry and Molecular Biology; see page 29 CLICK HERE 

    1. Cell Division and Insulin Action  Growth factors such as insulin and progesterone induce Xenopus oocytes to divide to produce eggs but we do not know exactly how.  Insulin, of course, is also involved in regulation of glucose levels in the blood stream and insulin resistance is involved in diabetes.

More specifically, insulin, progesterone, or IGF-1 addition to the Xenopus oocyte induces the oocyte to undergo meiotic cell division to produce the fertilizable egg. Click here to see a figure of the biochemical paths for hormone-induced meiotic cell division. insulinClick to see an ANIMATION of the activation of PI turnover and calcium release (requires Shockwave player; click on line at bottom of this page to download software) in the induction of meiotic cell division in the Xenopus oocyte.  Click for further discussion of the role of intracellular calcium in the induction of meiotic cell division.
            Related to this work on the insulin receptor, we can also study the mechanism of action of insulin and the anti-diabetic drug metformin (Glucophage; click here for 1998 paper on metformin.) WE BELIEVE THAT THIS MAY BE THE FIRST CLINICAL ARTIFICIAL ACTIVATOR OF TYROSINE KINASES.  Other work involves a demonstration of tyrosine kinase activation by both insulin and progesterone, and that this activation is required for phospholipase C stimulation.

For a YOUTUBE video of manual dissection of the Xenopus oocyte, click here.

    2. Fertilization  We still do not know how the sperm merges with the egg or how the sperm activates the egg.from: http://www.biochem.missouri.edu/~lesa/LIPIDS/lipid.htmlWe believe that LIPIDS (see molecule to right) may enable both these processes, so we study lipid changes that occur during fertilization. Click here for summary of three papers on role of phospholipase C (and IP3 production) in fertilization.  We have quantified the major phospholipid classes (click here for study of phospholipid changes at fertilization), found that diacylglycerol increases at fertilization,  suggest sphingomyelinase activation at fertilization and quantified lipid-dependent protein kinase C activation.

For an ANIMATION of the oocyte to egg maturation and events of fertilization, click here (34 K Shockwave animation; see bottom of this page to download Shockwave player).

Our CURRENT MODEL for fertilization is that a lipid (called PA) is important in sperm-egg fusion and the release of calcium.  Click here to view a FLASH ANIMATION that also suggests that IP3 (not Ca, or PLC) diffuses to produce the calcium wave at fertilization.  We are currently examining whether PA directly activates phospholipase C (PLC) or acts through stimulation of Src tyrosine kinase; view a PowerPoint animation by clicking here (THEN click on "OPEN" and click anywhere on the PowerPoint image to start animation).  We are also examining the role of this lipid PA in the acrosome reaction of sperm.

A major Fertilization event: after sperm-egg contact is the propagation of a slow Calcium "wave" from the sperm entry point to the opposite side of the cell (for a list of fertilization events in Xenopus fertilization, and their time of occurrence, click here). This wave of elevated calcium inside the cell is associated with a wave of contraction of the cell's surface and a wave of cortical granule exocytosis (CGE). The chemical links between the zygote and the fertilization envelope are broken due to enzymes released during CGE (along with destruction of sperm binding molecules located at the egg surface).  So, after CGE, the egg rotates freely within the egg jelly and the heavier yolk side rotates so that it is on the bottom--this is gravitational rotation). Click here for two VIDEOS of these fertilization events..  To see a third VIDEO of a group of zygotes undergoing GRAVITATIONAL ROTATION, click here.

Another fertilization event: there is a transient contraction of the animal pole...pigment granules (most are located just under the plasma membrane) move toward the dark animal pole.  Click here to view before and after pictures of fertilization showing this movement.

Ionophores are molecules that allow the Calcium ion to move across membranes- they can mimic sperm in that when an ionophore is added to an egg, it causes an increase of Calcium in the cytoplasm and this artificially activates the egg (parthenogenesis) and induces numerous fertilization events (the egg will start development but typically the cell dies due to lack of sperm genome and since sperm may induce other events).  View a Shockwave video of addition of 10 ÁM A23187 (an ionophore) to Xenopus eggs- CLICK HERE. Look for the labels in the upper left corner for time after addition of ionophore and note the changes that take place in the dark animal pole at about 28-20 min.  This experiment is one of many that support the idea that fertilization is largely due to an increase in Calcium in the cytoplasm. Video taken by Tim Silverstein (who is now in a Ph.D. program at Mount Sinai School of Medicine, NYC, in Molecular, Cellular, Biochemical, and Developmental Sciences).

At about 1 and a half hours after insemination, the first CLEAVAGE FURROW begins. To view a VIDEO, click here. What type of cleavage pattern does the Xenopus embryo show?  (holoblastic, radial; and egg is mesolecithal). 4 cell Xenopus embryo:

POLYSPERMY: Fertilization in NaI (Grey 1982 paper) causes more than one sperm to enter the egg...each one starts the cleavage process -see photos CLICK HERE.                                                                           

Why do we use frog oocytes and eggs instead of cells from humans?

Click here for OTHER REALLY INTERESTING WEB SITES. (Covering Xenopus biology, oocyte maturation, fertilization and embryogenesis)

"This material is based upon work supported by the National Science Foundation under Grant No. 9631051." "Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation."


Go to Univ. Colorado-Denver Biology Dept. home page

Click here for Shockwave Plugin that is Required to View the Animations