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Dr. Lemmon


 
Research Interests

  

 

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Laboratory

 

 

One on One Video

 


Contact Information:


 

The Miami Project
to Cure Paralysis

 

1095 NW 14th Terrace

 

Locator Code R-48

 

Miami, Florida 33136

 

 

Tel:  (305) 243-8184
Fax: (305) 243-3921

 

 

vlemmon@med.miami.edu


 

Home Our Research Faculty > Vance Lemmon, Ph.D.

 

VANCE LEMMON, PH.D.

Walter G. Ross Distinguished Chair in Developmental Neuroscience
Professor, Department of Neurological Surgery

 

 

High Content Screening and Functional Genomics of the Nervous System 


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    Research Interests

    Vance Lemmon, Ph.D.

     

    The mass of information available from the various genome projects, together with sophisticated image analysis and laboratory automation has created an opportunity to revolutionize the study of the nervous system. Our laboratory has developed methods to test hundreds of genes in hundreds of thousands of neurons each week and obtain quantitative information about cell morphology and gene expression. This “high throughput” capability allows us to tackle questions about development and regeneration using Systems Biology approaches. The biological problem we have focused on for the past six years has been to uncover genes that promote or prevent axon regeneration.

    The Lemmon-Bixby lab has four ongoing projects related to axon regeneration. The first project springs from the fact that neurons in the peripheral nervous system are able to regenerate while neurons in the central nervous system (CNS) are not. By analyzing data from several molecular biological approaches we were able to identify 900 genes that are preferentially expressed in regenerating peripheral neurons; of particular interest is a sub-list of 40 transcription factors (TFs) that are likely to regulate expression of other genes. The top TF has been confirmed to enhance neurite growth when over-expressed in CNS neurons.

    Our second project is based on the fact that young CNS neurons have a greater regenerative capacity than old CNS neurons (collaboration with Dr. Jeff Goldberg). We have used DNA microarray data to generate a list of 800 candidate genes. We have tested about 60% of the genes on our list, and have identified 4 TFs that have a robust effect on neurite growth: two enhance growth and two inhibit growth. Interestingly, the two TFs that enhance growth show decreased expression as development proceeds, and the two that inhibit axon growth show increased expression as the animal ages.

    The third project is to test effects of overexpression of known signaling proteins (kinases and phosphatases). In this screen we have tested 724 genes, and have found a high percentage with significant effects on neurite growth (about 40 total). The data from this screen is allowing us to begin to build models of neuronal signaling networks underlying axon regeneration. We are also using cheminformatics (collaboration with Stephan Schuerer) to identify chemicals that alter the activity of the interesting signaling molecules.

    The fourth project is to screen a chemical compound library to identify compounds that can overcome the regeneration-inhibitory effects of the injured CNS (collaboration with Prof. Young-Tae Chang, , National University of Singapore). We have identified four compounds that enhance axon growth of a variety of neurons in inhibitory environments. One of these has been found to enhance regeneration in an acute spinal cord injury model in vivo.

     

    Q & A with President, Marc Buoniconti

    Today we’re talking with Dr. Vance Lemmon, Ph.D., the Walter G. Ross Distinguished Chair in Developmental Neuroscience. He’s been part of The Miami Project team since 2003 and brings a wealth of knowledge to our team. He makes up half of the LemBix lab, with Dr. John Bixby, which was instrumental in identifying a new family of genes that regulate nerve growth. See the In the News from October 9, 2009. www.themiamiproject.org/Page.aspx?pid=653 In my opinion, their work is some of the most cutting edge and exciting currently underway at The Miami Project and the University of Miami.

    Marc: Dr. Lemmon, when did you first start thinking about research?

    Dr. Lemmon: Since I was in the 4th grade. I wanted to be a scientist forever. I used to watch Jacques Cousteau and I wanted to be a marine biologist. As a kid I went to marine biology summer camp on Catalina Island and learned how to scuba dive when I was thirteen. I grew up in the desert close to Los Angeles so of course I wanted to be a marine biologist.

    Marc: So how did your interest in marine biology turn into neuroscience?

    Dr. Lemmon: I went to the University of California San Diego because they have a great marine biology program there. I started taking neuroscience courses as an undergraduate and I got very interested in that area, so that’s how I shifted over from marine biology. They didn’t have neuroscience Ph.D. programs when I went to graduate school so if you wanted to do neuroscience, you basically went to anatomy or physiology departments. I got a Ph.D. in anatomy from Emory University studying neuroanatomy and neurophysiology and then went to Washington University in St Louis where they have great neuroscience programs.

    Marc: Did you know the Bunges at the time?

    Dr. Lemmon: I did know the Bunges. In fact, I worked in another lab but we collaborated with the Bunges so I’ve known Mary Bunge since about 1979.

    Marc: Where did you go after St. Louis??

    Dr. Lemmon: When I was at Emory I was studying the visual system and when I left to go to Washington University, I started studying the development of the visual system. After about a year I finished the project that we thought would take a couple of years and so I changed labs and started studying the cell biology of how nerve cells migrate and axons grow. I learned how to use monoclonal antibodies, which at the time were the new thing. Monoclonal antibodies are cool because it is possible to make a very specific marker for a protein or cell without first having purified that protein. Even now it is hard to purify proteins, so we still use tricks to make monoclonal antibodies that then allow us to study specific proteins in cells and in the brain.  Then I got my first job in Charleston, SC. After a few years I moved with my Department Chair to Pittsburgh where we stayed for five years. Then I moved to Case Western Reserve University in 1988 with my wife, who was seeking a tenure track job and it turned out to be good for both of us.

    Marc: When was the first time you heard of The Miami Project and what made you want to be a part of it?

    Dr. Lemmon: I think I first heard of it when the Bunges moved down. Personally I wasn’t applying for jobs at the time but one day I got a phone call from Dr. John Bixby and he said they have these job openings down here and he wanted me to apply. I went home and asked my wife if I could apply and she said you’ll never get the job so sure, you can apply….. I’m not making this up. That is the truth. So I applied and came down and gave a talk and talked to Dr. Dietrich on that visit and then I came down for another visit was talking more with Dalton and some others from the research team and I could see how what I was doing was a much better fit here at The Miami Project. I’m always full of wacky ideas and I said, let’s try and get Bixby together with me and we were able to put this bigger idea together and that was very cool.

    Marc: So now that you are here for a few years, how have things worked out for you in your lab?

    Dr. Lemmon: It’s actually quite amazing. I brag about it all the time. When I talk to people, I talk about how amazing my experience has been in The Miami Project. I was lucky because John (Bixby) and I get along so well. We’re two different people, but we have really common goals. We have a good synergy and the resources we’ve gotten from being able to work here have allowed us to tackle really big problems that we would have never been able to do anywhere else. I think that we’ve made amazing progress and so it’s very exciting for me to be a part of this and work with some really smart, young people that I would have never been able to recruit at my previous institution. It’s easy to sell The Miami Project and Miami to young people to get them to come and work here, so that is a huge advantage.

    Marc: What excites you the most?

    Dr. Lemmon: We have all these interesting genes from our big screens, where we have tested over 3000 genes for their ability to influence nerve growth, that we can now start testing in vivo. For the last year we’ve been working hard to develop in vivo methods using viruses so we can insert growth promoting genes into neurons and also prevent the expression of growth inhibiting genes. 

    I am also excited about extending our in vitro studies. Before I came down here to talk to you I was with Dr. Murray Blackmore and we were looking at new microarray experiments that we’ve done with Jeff Goldberg’s group in Ophthalmology. Last year we published a paper on how the KLF family of genes can turn axon growth on and off. Now we are using microarrays to discover how the KLFs control axon growth by turning on and off other genes.   This should give us new candidates to test for influencing axon regeneration.

    It’s exciting to be a part of the rapid growth of the Miller School of Medicine under the new Dean. He recruited Peggy and Jeff Vance and their colleagues from Duke to create and instant human genomics institute. He also helped create the Center for Computational Sciences, which I am now a part of. We have access to supercomputers and, more importantly, the people who know how to use them. Quite simply, there’s a lot of things we would not be able to do, even at The Miami Project, had these other groups not been brought in to the University. It’s pretty cool that we’re using next generation sequencing techniques to look at these big changes in neurons that can regenerate versus the ones that can’t. That’s very exciting. I tell everybody all the time that I have the coolest job in the world.

    Marc: We’re always so focused on clinical trials and science that can translate to the human condition. What do you think the best application is going to be for your work?

    Dr. Lemmon: Our group studies the genes that can enhance or inhibit regeneration. When we identify interesting candidate genes or pathways we can then go after compounds that we can use to turn those genes on or off. This is because I think using gene therapy in human spinal cord and brain is going to be difficult for some time. Specific compounds should be easier to develop into therapies. One of our postdocs is working on this now. It was also my main motivation to work with Stephan Schurer in the Center for Computational Sciences on a project about data mining of information from bioassays in the NIH databases for which we were awarded an NIH Grand Opportunity grant last fall.

    Marc: So eventually we’ll be able to take these compounds and combine them with Schwann cells that we are already working with to try and enhance regeneration?

    Dr. Lemmon: Yes, I think it will be combinations. I think the Bunges are right.   We’re going to have to try different kinds of combinations. But already we have lots more candidates like the KLF’s and the PTEN pathway found in Zhigang He’s lab at Harvard to promote regeneration that didn’t exist two years ago.

    Marc: That is truly exciting. Just think how much more we’ll know two years from now. Thanks so much for your time and for telling us a little about you and your work.

     

     

     

     
     
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