CURRENT PROJECTS
01
Gene therapy for the prevention Phantom Limb Pain
[Ser1]histogranin (SHG), demonstrates inhibitory properties at the NMDA receptor and can reduce pain. Studies in our lab have shown that injection of viral vectors producing SHG can reduce pain symptoms following peripheral and CNS injury in rats. Further, we have found that the addition of a potent mu-opioid peptide, endomorphin-1 (EM-1), provides additional synergistic antinociception. The goal of these studies is to determine optimal therapeutic windows and routes of administration of SHG/EM-1 gene therapies in a rat model that replicates clinical scenarios of amputation-like injury
02
Alleviation of chronic spinal cord injury pain using recombinant GABAergic cells
Previous findings in our lab have shown that analgesic peptides such as SHG, EM1 and MVIIA can reduce chronic pain when delivered via gene therapy or engineered neural progenitor cell transplantation. The goal of these studies is to further develop these strategies towards clinical translation by evaluating the ability of human induced pluripotent stem cells (hiPSC)-derived transplantable cells to reduce SCI pain and produce SHG and EM1. We also aim to develop transplantable recombinant GABAergic cells that release MVIIA, a N-type Ca2+ channel antagonist to alleviate pain-like behavior following peripheral and spinal cord injury.
03
Alleviation of chronic SCI neuropathic pain using novel engineered human iPSC-derived chromaffin cell grafts
Cell transplantation can provide sustained, targeted, and customized delivery of analgesic compounds. Using hiPSCs techniques, cells of various phenotypes can be autologously derived from the patient’s own cells. Specifically, we are interested in adrenal medullary tissue or isolated chromaffin cells as they have shown efficacy in various pain models. Thus using a rat SCI model, our aims are to 1) develop hiPSC-derived adrenal chromaffin cells for transplantation 2) optimize their long-term survival using using custom and 3D bio-printed matrices and 3) engineer these cells to produce synergistic analgesic peptides for enhanced pain relief. In the future we hope to also explore the analgesic potential of these transplant in other pain models such a low back pain and arthritis.
04
Cell transplantation and exercise for the treatment of chronic SCI pain
Work in our lab has shown mutually beneficial effects of GABAergic rat neural progenitor transplants (NPCs) in combination with a locomotor exercise protocol in reducing chronic SCI pain. Underlying the beneficial effects of this strategy, our results suggest markedly reduced spinal cord inflammation and partial restoration of dorsal horn inhibitory GABAergic function. In addition, previous findings in our lab have demonstrated enhanced NPC survival and function in the rat brain when co-transplanted with trophic factor-producing adrenal medullary chromaffin cells. Together, these combination strategies may provide enhanced pain alleviation and functional restoration following SCI.
05
Targeting cannabinoid receptors for treatment of chronic SCI pain
Although CB1 receptor antagonists have been shown to have strong analgesic effect their clinical use has been hampered by their potential psychoactive effects. The goal of these studies is to identify and develop potent local delivery approaches using cannabinoidergic peptides derived from venom extracts of marine cone snails.
06
Cannabis constituents for the treatment of chronic pain
The most frequently reported use of medical marijuana is for pain relief. While the best studied cannabis component for pan alleviation is THC, other major components have been reported to have beneficial analgesic or anti-inflammatory effects including CBD and BCP (β-caryophyllene). The goals of these studies were to evaluate these components and their combinations for 1) the ability to reduce pain in a SCI model and 2) their ability to prevent or reverse phantom limb pain. We found that when combined additive or synergistic effects could be achieved for the alleviation of neuropathic pain. In the future, we hope to administer these synergistic doses using a exosome delivery platform.
07
​
RNA aptamers as analgesic candidates
In this project we are testing three RNA aptamers that act as AMPA or kainite receptor antagonists. Although studies have shown that AMPA/kainate receptor antagonists can inhibit pain, most existing AMPA receptor inhibitors have reduced CNS bioavailability due to poor water solubility or off target effects from systemic administration. By delivering these aptamers intrathecally we hope to test a new class of potential analgesics in a rat SCI-induced pain model.