Faculty Profiles

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Raymond J. Grill, PhD

grill,-raymond.jpgAssociate Professor
Office: R715
(601) 815-1914
Email: rgrill@umc.edu

Education

  • BA, biolology, Kenyon College, Gambier, Ohio, 1988
  • BA, psychology, Kenyon College, Gambier, Ohio, 1988
  • PhD, cellular biology and anatomy, University of Cincinnati, 1995
  • Postdoctoral Fellow, Department of Neurosciences, University of California - San Diego, 1995

Research interests

  • Spinal cord injury
  • Traumatic brain injury
  • Neurodegenerative diseases such as amyotrophic lateral sclerosis

Current research

My current research focuses on deriving a better understanding of the acute-to-long term pathophysiologies that shape the environment of the spinal cord following trauma. Specifically, I am exploring the question of what makes the injured spinal cord so resistant to the development of effective treatments; designed to either preserve function when applied in the early phase of injury or restore function when treatment is delayed until the far chronic phase. Our studies have suggested that spinal cord injury creates an environment that shares similarities to many forms of cancer in which a type of chemotherapeutic resistance develops. Our studies have focused on attempting to better understand the mechanisms that drive this chemotherapeutic state in order to better prevent or suppress its occurrence. I am exploring similar questions in the area of traumatic brain injury and ALS.

Research program

Chemotherapeutic resistance in spinal cord injury

grill---image-1.jpgIt is an unfortunate fact that, despite decades of intense study and multiple clinical trials, there are no effective therapies that will preserve or promote the recovery of function lost to spinal cord injury (SCI). One of the primary areas of interest in my lab is to better understand the reasons underlying the lack of success in treating spinal trauma. We recently demonstrated, in a clinically-relevant rat model of SCI, that the injured cord responds to injury by upregulating expression of a protein previously shown to promote chemotherapeutic resistance in many forms of cancer. We subsequently demonstrated that this response effectively prevented the ability of a neuroprotective drug known to be a substrate of this protein, to successfully enter the cord. By targeting the molecular/biochemical pathways that regulate expression of this chemotherapeutic resistance protein, we were able to suppress its injury-dependent upregulation and enhance tissue bioavailability of the treatment. We are currently exploring the development of chemotherapeutic resistance throughout the body, the mechanisms that drive such a state, the role of chemotherapeutic resistance in shaping recovery from SCI and the development of novel approaches to suppress it.

Spinal cord injury and neuropathic pain

grill---image-2.jpgNeuropathic pain (NP) is an agonizing condition that afflicts up to 82% of patients who are living with an SCI with few effective treatment options. We are currently exploring the mechanisms underlying both the development and long-term maintenance of such pain as well as novel methods for either prevention or long-term suppression of NP using clinically-relevant animal models of SCI.

Spinal cord injury and male infertility

grill---image-3.jpgSCI can induce a profound state of infertility in men; taking away one of our most fundamental biological drives, reproduction. While the mechanisms that contribute to this state are poorly understood, we recently reported an SCI-dependent reduction in the blood-testis-barrier (BTB) the cellular specialization within the testes that isolates and protects developing sperm from immune exposure. We found that spinal trauma produces an early, but sustained state of inflammation and oxidative stress in the testes that coincides with a breakdown in BTB integrity; allowing infiltration of peripheral immune cells. We have also identified a novel therapeutic that suppresses these pathological events. Current studies are focused on translating this approach as a treatment to either prevent loss of fertility or restore fertility in both early and late stages of SCI.

Spinal cord injury and osteoporosis

grill---image-4.jpgIndividuals who suffer an SCI can develop a rapid and sustained loss of bone density that dramatically enhances the risk of fracture. As fractures often occur in bones below the level of cord injury, these patients may not be aware of bone damage; resulting in potentially fatal consequences. We are currently exploring the mechanisms underlying the rapid loss of bone density that follows an SCI with the goal of assessing novel interventions; such as the use of cannabinoid receptor modulators, in either preventing or reversing SCI-dependent osteoporosis.

Traumatic brain injury

grill---image-5.jpgTraumatic brain injury (TBI), like SCI, remains without an effective therapy to preserve or restore function. Using a novel rodent model of concussive injury, we are exploring the physiological mechanisms that contribute to pathological changes in cognition, memory, emotion and pain.

Current funding

  • Department of Defense SC140017
    Development of novel combinatorial treatment to prevent chemotherapeutic resistance and enhance efficacy of riluzole in a rodent model of SCI.
    PI: Grill
    09/01/15-08/31/18

Selected publications