DR. BRAD STITH, 
UNIVERSITY OF COLORADO DENVER, BIOLOGY HOME PAGE
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)
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1. Presentations on Undergraduate
Research at Clarion University (Oct. 10, 2008), |
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 |
|
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 |
|
4. Grant
Writing Skillswith emphasis in Biology (given at CUR National Conferences
2000, 2002, 2006) |
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 here. OUR 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. 
Click 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.
We 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 µM 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