Welcome to the Clark Lab website. We study protein evolution using caspases as a model system. Caspases are integral proteases in cell development and in programmed cell death (apoptosis). The dysregulation of apoptosis is observed in a number of human diseases, from autoimmune diseases (rheumatoid arthritis, diabetes), to neurodegenerative diseases, to cancer.
About 2.5 million deaths are registered in the US each year (www.cdc.gov). Heart disease and cancer account for about half of the deaths. The impact of chronic diseases (heart disease, stroke, diabetes, Alzheimer) on healthcare costs approaches $750 billion per year. Anticancer drugs are effective at inducing apoptosis by a variety of mechanisms because cancer cells are known to evade pro-apoptotic signals when compared to normal cells. Our goal is to understand how unique characteristics of caspase enzymes evolved to provide discrete cellular functions and how the enzymes are regulated under normal versus aberrant cellular conditions. Specific projects are described on the Research page.
The lab members (minus Dr. Clark) attended the 2019 Texas Protein Folding and Function conference in Cleveland, Texas. The mid-April meeting usually means very nice weather in Texas, and the conference is held in idyllic setting. Great talks on proteins and opportunities for students to network.
Suman presented his work on the evolution of caspase folding landscapes:
Suman – Texas Protein Folding and Function 2019
Slideshow of the weekend conference:
The University recently posted a press release on our new NIH grant:
Clark NIH grant
Dr. Clark and two graduate students – Liqi Yao and Suman Shrestha – attended the 2019 ASBMB conference in Orlando, Florida in May. The lab presented new results on coral caspase structures, the evolution of enzyme specificity, and the evolution of caspase folding landscapes.
We made some new friends:
And we saw a former lab member: Dr. Kakoli Bose:
It’s in the Syllabus
Welcome to the new freshman class and transfer students. Here are a few suggestions to make your college career successful. My list is not based on surveys or other scientific methods. Rather, I’ve noticed that students who are successful at University develop some or all of the following habits.
7 Habits of Successful Students:
1. Don’t Panic – The faculty and staff can help you solve your problems.
2. Pay Close Attention to:
- Syllabus – Many of the answers are posted in many places and in many ways.
- Course Calendar – a quick way to see when assignments are due.
- Announcements made in class and posted on the course page.
- Exam Schedule – Be prepared and on time. Don’t wait until the day before the exam to study the course materials.
Dr. Bob Grinshpon developed the CaspBase, a curated database with over 2,000 sequences of caspase proteins from over 360 taxa. Bob’s paper describing the database is now in press at Protein Science and is titled: The CaspBase: A curated database for evolutionary biochemical studies of caspase functional divergence and ancestral sequence inference.
Using data from the CaspBase, we describe the utility of the database by analyzing levels of sequence conservation among caspase homologs, and we discuss how the CaspBase lends itself to evolutionary biochemistry and ancestral protein reconstruction (APR) analysis of common caspase ancestral proteins.
The database is available at CaspBase.org
Melvin’s recent JBC paper was the subject of this recent interview in ASBMB Today. Melvin showed that an evolutionarily conserved phosphorylation site in caspases uses a common allosteric network to decrease the activity of caspase-3. A mutation in mammalian caspase-3 introduces a kill-switch into the enzyme so that it is turned off when the site is phosphorylated.
Melvin’s paper was published recently in the Journal of Biological Chemistry.