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Trainee Highlights

 

 

Dario Motti, Ph.D., a post-doctoral fellow with Dr. Vance Lemmon, received the award for the Best Poster at the 2012 “Applying Next-Generation Sequencing” meeting held August 13-15 in Providence, RI.   The title of his award winning poster was “RNA‐Seq and microRNA expression profiling reveal networks of RNA interactions in regenerating dorsal root ganglion neurons”.   


The studies in the Lemmon-Bixby lab focus on axonal regeneration.  In this particular study, Dario took advantage of Next Generation Sequencing of the Transcriptome (RNA‐Seq) to identify mRNA isoforms differentially expressed in the neurons of the dorsal root ganglion (DRG) after sciatic nerve crush, an injury that is known to initialize the axonal regeneration program in these neurons. The expression of different RNA species is influenced by and influences the activity of small regulatory RNAs (e.g. microRNAs).  They identified more than 2000 mRNA isoforms and more than 40 microRNAs that were differentially expressed in DRG neurons 7 days after axotomy.  Their approach revealed, for the first time, differential expression on an isoform specific basis. Among the microRNAs, they observed downregulation of mir‐9, a neuronal specific microRNA whose inhibition increases axon length in cortical cells.  They are currently using a bioinformatic approach to predict the interactions among these mRNAs and microRNAs, and thus to describe the regulatory network behind the transcriptional profile of regenerating DRG neurons to further our understanding of the genetic mechanisms underlying the process of axon regeneration.

At the same meeting, Dr. Lemmon gave a featured talk entitled “Using RNA-Seq to Uncover Isoforms and Molecular Networks Involved in Nerve Regeneration” and chaired a session about “Conquering the Cancer Genome”.

In addition to winning the best poster, Dario also gave a 15 minute talk and led a discussion session about “Defining the transcriptional landscape through RNA-Seq: from reads to isoforms.”  Talk about multi-tasking!  Congrats Dario!!

 


 

 

Meghan O’Connell Blaya, a Ph.D. graduate student in the laboratory of Dr. Dalton Dietrich, was selected to participate in the Top Student Finalist Competition at the National Neurotrauma Society annual meeting held July 22-25, 2012, in Phoenix, AZ.  She received an award for her poster entitled “Transplantation of genetically-modified neural progenitor cells releasing a chimeric neurotrophin leads to increased cell survival and targeted migration after traumatic brain injury in the rat”. 

 

These studies were evaluating the idea of transplanting neural progenitor cells (NPCs), which have been genetically modified to secrete a multi-neurotrophin that can bind all tropomyosin-receptor-kinase (Trk) receptors, as a neuroprotective and reparative strategy for traumatic brain injury (TBI).  They transplanted these cells near the lesion area in a rodent model of TBI.  They found that these cells have increased survival and targeted migration five weeks after transplantation. Sham animals receiving the cells did not exhibit similar targeted migration patterns; however, exogenous cell survival was evident. NPCs exhibit tropism towards areas of injury, which may explain why only TBI animals had significant NPC migration. The majority of transplanted cells colocalized with NeuN-positive cells, indicating that these cells differentiate primarily into mature neurons.  Interestingly, all animals receiving NPCs performed on par with sham uninjured animals in a spatial memory task, while the TBI/Vehicle group had significant learning deficits. Cellular transplantation coupled with multineurotrophin exposure represents a novel combinatorial approach to attenuate cognitive impairment after TBI. Meghan will continue with these studies to determine if this multidimensional intervention may be more effective in improving outcome than one-dimensional therapies alone.

 


 

 

Yang Liu, a Ph.D. student in Dr. Christine Thomas’ lab, received student travel awards to attend the 11th International Neural Transplantation & Repair Conference held at Clearwater, FL in May, 2011 and the Society for Neuroscience 41st Annual Meeting in Washington DC in November 2011. At these conferences, he presented posters on his research related to use of electrical stimulation of embryonic transplants in peripheral nerve to improve muscle function.

This research addresses the clinical issue of rapid and progressive muscle denervation that occurs after motoneuron death, a common phenomenon with spinal cord injury or motoneuron disease. In his study Yang showed that there are long term benefits to electrical stimulation of the replacement neurons. With just one hour of electrical stimulation of the transplanted rat embryonic day 14-15 ventral spinal cord cells, more axons had grown from the transplanted cells 10 weeks later. Further, more muscles contracted upon transplant stimulation compared to control and this reinnervation reduced muscle atrophy significantly. The combination of neuron transplantation and a brief period of electrical stimulation therefore provide an important long-term strategy to rescue muscles from atrophy following motoneuron death. Muscle reinnervation also dramatically improved the excitability of skeletal muscles, opening the possibility of artificial control of muscles through patterned electrical stimulation.

 


 

Dr. Xie was a Postdoctoral Associate (Feb 2008- March 2011) in Dr. Brian Noga’s lab here at The Miami Project to Cure Paralysis.  Research in this laboratory is concerned with understanding the control of spinal locomotor neurons by descending monoaminergic pathways originating within the brainstem.  Monoamines hold particular promise as transmitter replacement candidates for facilitating walking following spinal cord injury.  Dr. Xie was a perfect candidate for this position having just finished his Ph.D. at Case Western Reserve University, School of Engineering where he worked on the development of diamond-tipped microelectrodes for the detection of monoaminergic neurotransmitters in brain tissue.  During Dr. Xie’s tenure in Dr. Noga’s laboratory, he played a major role in the development of a new experimental model to study spinal transmitter release during walking.  The research has led to new insights on the mechanisms of spinal monoamine release and the effects of other major transmitters on this release.  The results are highly significant and will greatly enhance our understanding of transmitter dynamics and their interactions during the production of walking.  Results of this study have important implications for the design of transmitter replacement strategies which aim to alter transmitter levels within the spinal cord and facilitate walking in persons with spinal cord injury.  In late 2011, Dr. Xie took a new position as a Senior Engineer in the Department of Neurological Surgery at the Mayo Clinic in Rochester, MN.  There, he is mainly involved in the development of chronic implantable, flexible electrode arrays for the Mayo Neuromodulation System to advance deep brain stimulation and brain-machine interfacing techniques.  By providing an interface for real time neurotransmitter monitoring, electrical stimulation and recordings, such a close-loop electrode device can serve as a neural prosthesis with chemical and/or electrical feedback.

   



 

Jessica Ashbaugh, a Ph.D. graduate student with Dr. John Bethea, received a 2012 American Association of Immunologists (AAI) Abstract Trainee Award for the upcoming 99th AAI Annual Meeting - IMMUNOLOGY2012TM – to be held May 4 – 8 in Boston, MA.


This was for her studies detailing the role of Interleukin-7 receptor α (IL7R α) in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). She found that IL7Rα defective mice display a less severe form of EAE; particularly they had reduced levels of paralysis, myelin damage, and inflammation. Furthermore, diseased wild type mice that were treated with neutralizing anti-IL7Rα showed significant recovery in EAE clinical scores and reduced lymphocyte infiltration into the central nervous system. Together with other results, she demonstrated that IL7Rα signaling blockade in multiple cell types is necessary for marked reductions in EAE. This could be considered as a new therapeutic target for MS worthy of additional investigation. Her abstract, titled “Interleukin-7 receptor α contributes to experimental autoimmune encephalomyelitis”, was chosen for oral presentation. Congratulations!
 


 

A hearty “Congratulations” to Stephanie Bacik on receiving the outstanding news that her NIH Pre-doctorial Fellowship Application will be funded on the first submission! Stephanie is a graduate student in the Neuroscience Program, and is working in Dr. Robert W. Keane's lab in the Department of Physiology and Biophysics. Stephanie is studying the innate immune response following traumatic brain injury (TBI).

 

TBI affects an estimated 1.5 million people each year and contributes to one third of injury-related deaths. It is well known that the initial injury is exacerbated by a robust and poorly controlled inflammatory response, which contributes to secondary cell death in areas of the brain distant to the initial trauma. The innate immune response to tissue injury is mediated, in part, by the inflammasome, a multiprotein complex that senses endogenous danger signals and is responsible for caspase-1 activation and the production of inflammatory cytokines. The AIM2 (absent in melanoma 2) inflammasome is the most recently identified, and least understood, inflammasome complex. The AIM2 inflammasome is activated by dsDNA and has been characterized in macrophages, predominantly in the context of viral infection. However, the AIM2 inflammasome also responds to self-DNA and induces pyroptosis, a recently-characterized, inflammatory cell death program. Stephanie’s central hypothesis is that AIM2 forms an inflammasome in neurons, is activated by endogenous dsDNA released from necrotic cells following TBI, and contributes to caspase-1 activation, inflammatory cytokine production, pyroptotic cell death, and injury pathology. These studies will increase our understanding of secondary neuronal death and the innate immune response following TBI, and aid in the identification of a novel therapeutic target to limit the chronic, progressive loss of neurons following brain injury.

 


 

 

Michelle Theus, a post-doctoral fellow with Dr. Dan Liebl, received the “Women in Neurotrauma Research Award” at the 2010 National Neurotrauma Society Annual meeting! This was for her studies detailing the role of Eph receptors in the control of neural stem cell proliferation/expansion in the brain following injury. These studies are critical to advancing our understanding of how to harness adult stem cells and learn how to use them effectively to try to repair the spinal cord or brain after injury. Here is a photo of Michelle receiving her award from Dr. Geoff Manley, President of the National Neurotrauma Society. 

 


 

Matthew Sacino, University of Miami undergraduate, is an achiever and the Miami Project is proud to be a part of his education! Matt has been volunteering in the laboratory of Drs. Vance Lemmon and John Bixby for a couple years now. Under their guidance, he has performed research on axonal regeneration in the central nervous system at the Lois Pope LIFE Center. He recently received Honorable Mention from the Barry M. Goldwater Scholarship and Excellence in Education Program. Sacino was recognized on the basis of academic merit and from a field of 1,111 mathematics, science, and engineering students who were nominated by the colleges and universities nationwide. The Scholarship Program honoring Senator Barry M. Goldwater was designed to foster and encourage outstanding students to pursue careers in the fields of mathematics, the natural sciences, and engineering. The Goldwater Scholarship is the premier undergraduate award of its type in these fields.


Matt was also selected as a member of USA Today’s All-USA College Academic First Team. Only twenty undergraduate students in the entire country are on this list each year! These winners “defy expectations”. “At their core, they are solution-oriented thinkers who aren't afraid to dare. And in defying standard notions of what it means to be a student, they set a high bar for what the undergraduate experience looks like.” Selected by a panel of judges from among hundreds of college juniors and seniors, first-team members received a $2,500 cash award.

Sacino, a Neurobiology and Chemistry major, is the founder and editor of the UM Undergraduate Research Newsletter (URN) and Vice President of the Undergraduate Neuroscience Society. He founded a program to collect unused medical supplies from Miami-area hospitals and clinics and, partnering with Project Cure, ship them to facilities in developing countries. He helped establish, organize, and screen applicants for the volunteer program at the University of Miami Hospital. This summer he is working with Dr. Murray Blackmore and studying a set of transcription factors called KLFs that play a large role in regulating neuronal growth. Recently he has been focusing on the mechanisms by which these transcription factors regulate activity, such as DNA binding activity and post translational modifications. They are working to illustrate their in vitro model through in vivo experiments. He plans to obtain his M.D./Ph.D. in Cellular/Developmental Neuroscience and conduct research on neuropathological diseases.

 


Many women are making Miami a better community. But just four of them were recognized as emerging leaders in The Miami Herald's recent 20 under 40 contest. The small number motivated us to find women who are making a difference in our city and highlight their accomplishments. This month we nominate Dr. Rachel Cowan as an emerging leader. At 32, she's helping people with spinal-cord injury (SCI) maximize their ability to live and travel independently.

At the Miami Project to Cure Paralysis, Cowan does research to equip people with SCI  with physical conditioning and assistive technology so they can maximize their potential and live full lives. People with disabilities still face many barriers to achieving their optimal fitness. Her expertise in physical education and exercise science and her personal experience with spinal-cord injury have honed her ability to lead in this area.

With a Ph.D. in rehabilitation science and technology, Cowan helps clinicians determine the best assistive technology and fitness options for patients with SCI. In developing research initiatives, she asks: "How could this project help someone get the treatment/equipment that will help maximize their function?''

This fall, Cowan will give the plenary lecture at the Academy of Spinal Cord Injury Professionals. Her long-term goals involve changing policies and laws to make the world better for persons with mobility disabilities. One of her favorite quotes is from Robert Schueller: ``What great thing would you attempt if you knew you could not fail?''

Cowan wants to be a game-changer. She envisions using the path of academia to garner respect and credentials to create the largest possible impact. She wants to remove the barriers and frustrations she encountered since her injury so that others need not fight the same battles.

 

From The Miami Herald, June 20, 2010: Read more 

 

 

“Rachel also received the Fritz Krauth Memorial Fellowship for her new grant funded by the Paralyzed Veterans of America (PVA) Research Foundation 2010 grant cycle." For more details read here

 


 

Katie Gant, a research associate in the lab of Dr. Christine Thomas and Ph.D. student in the Biomedical Engineering department at the Un iversity of Miami, received a travel grant to attend a conference in Paris, France. This award was part of an NIH grant written by CJ Heckman at Northwestern University in Chicago. The biennial meeting, this year titled “Towards translational research in motoneurons”, brings together researchers from around the world that focus on motoneuron studies in animals and human subjects. Katie presented work from the Thomas lab in a poster titled “Long-term EMG records: muscle activity in healthy subjects”. She also chaired a session on “New techniques to investigate motor unit properties in humans”. Katie’s poster presented 24 hour EMG records from healthy subjects,

which will serve as important control data and is an important step towards interpreting data from people after SCI.   

 

 


 

Mousumi Ghosh, Ph.D. received the first inaugural “Young Investigator Award” from the Sam Schmidt Paralysis Foundation in partnership with the American Spinal Injury Association (ASIA) Sell Research Fund on September 25, 2009. The $15,000 award is designed to provide funding to a post doctoral researcher whose work has contributed substantially to the field of spinal cord injury medicine. Ghosh’s project entitled, “Addressing the Technical Limitations of Studying Axonal Regeneration in a Clinical-Relevant Contusive Spinal Cord Injury Model through Ex Vivo 3D Ultramicroscopy” focused on the use of three dimensional microscopy, a new state-of-the-art imaging method, for assessing the changes that occur during axon regeneration. Previous equipment was only two dimensional which didn’t allow it to be known if axons had regenerated from injury, whether they had been spared, or if they were the result of sprouting. The project answers the following questions:

 

1. Which axons are injured and which ones are spared?

2. What effect do Schwann cells implanted into the injured spinal cord have?

3. What impact will this method have as a research tool for the SCI community in the future?

 

“We are extremely excited to support this award in its inception,” said Ida Cahill, President of the Sam Schmidt Paralysis Foundation. “The invaluable research that these individuals engage in brings us one step closer to finding a cure for paralysis.”

A native of India, Dr. Mousumi Ghosh received her undergraduate degree from the University of Poona in Pune, India and graduate education from the University of Calcutta in Kolkata, India. She was nominated by Dr. Damien Pearse, her mentor at the University of Miami where she currently a postdoctoral associate.

 


 

Sarah Bobker was accepted into the 2010 Miami Project Summer Student Research Program. She has been working in the lab of Dr. Nancy Brackett on three projects:

 

1. Effect of brief high temperature exposure on sperm motility in men with SCI.
2. Comparison of processing methods on recovery of total motile sperm in men with SCI versus controls.
3. Comparison of the Miami Project Male Fertility Research Program database with other national databases in levels of injury and causes of injury.

Sarah is not your typical undergrad, she has just been admitted early to Tulane’s School of Medicine after completing only two years of undergraduate education! Premedical students usually complete the necessary four basic science prerequisites (Biology, Inorganic Chemistry, Physics, and Organic Chemistry – all with labs) by the end of their third year in college. However, choosing to accelerate her course load by doubling up two of these rigorous courses per year, Sarah has taken advantage of an early application process that Tulane offers to few undergraduate sophomores who meet certain high standards. She has succeeded in doing so! This guarantees her a slot in their 2012 class. However, it does not preclude her from applying to other medical schools. Her summer research with the Miami Project has fueled her interest in applying to the UM Miller School of Medicine as well. In the next two years, Sarah plans to broaden her creative intelligence as she completes a major in Dance and a minor in English. Furthermore, she is excited to maintain her knowledge of, and passion for, science (this time though by undertaking only one science class a year). She can now breathe a little easier knowing that her hard work has paid off and her dreams of becoming a doctor will one day be achieved!

 


 

Yenisel Cruz-Almeida, a doctoral student with Dr. Eva Widerström-Noga, recently received a Department of Veteran Affairs, Office of Academic Affiliations Predoctoral Associated Health Rehabilitation Research Fellowship award entitled “Functional integrity of somatosensory pathways in central neuropathic pain conditions after spinal cord injury.”

The purpose of this fellowship program is to facilitate doctoral level research with direct relevance to the rehabilitation of Veterans with disabilities and to enhance rehabilitation research capacity within VA. Providing an opportunity for interested students to develop expertise in clinical research will prepare fellows to assume leadership roles in rehabilitation research after receiving doctoral degrees. The fellowships are designed for graduate students who have completed doctoral course work in a rehabilitation-related health discipline, broadly defined, and who are prepared to work on basic science or clinical dissertation research relevant to recovery of function from disabling diseases or injuries of Veterans.

Yenisel’s application takes a multidisciplinary approach to study the complex pain conditions experienced by persons after a spinal cord injury (SCI). The goals of this research are to elucidate the relationship between the functional integrity of somatosensory pathways and the metabolic activity in the thalamus in persons after SCI. Specifically, relationships between the characteristics of chronic neuropathic pain associated with SCI, mechanisms of sensory function, and metabolite levels in the thalamus will be evaluated in persons with SCI with and without pain. Two non-invasive methods: Magnetic Resonance Spectroscopy (MRS) and Quantitative Sensory Testing (QST) will be used to address the study hypotheses.

 


 

 
 
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