Uche Maduka

Mentor: Donna L. Hammond, PhD

Year Entered Into Program: 2007

PhD Institution: University of Iowa, 2013

Affiliations

  • Pharmacology

Research Description

Chronic pain caused by various diseases affects 50 million people within the US alone, probably billions of people worldwide, but yet, mechanisms of chronic pain are still poorly understood. Long term potentiation (LTP) is a process by which synapses can change in transmission strength as a result of high frequency stimulation. Previous research has shown that LTP is dependent on calcium influx through the NMDA receptor (NMDAR) as well as activation of the Ca2+ / Calmodulin-dependent protein kinase II and its binding to subunits of the NMDA receptor. Earlier work in the laboratory of Dr. Hell has defined the binding sites for CaMKII on the NR1 and NR2B subunits of the NMDA receptor. We have also found that interfering with CaMKII binding to the NR1 and NR2B subunits inhibits hippocampal LTP and memory. Recently, researchers have begun to appreciate the parallels between learning and chronic pain, as nerve injuries can lead to molecular changes within the spinal cord through processes very similar to LTP. It is our hypothesis that molecular and pharmacological ways that interfere with LTP will also inhibit the development of chronic pain. To test this hypothesis, we have developed mice with impaired CaMKII binding to the NR2B subunit of the NMDAR. Protein levels of CaMKII, NMDAR subunits and other postsynaptic proteins in these mice are comparable to those in wild type mice. These mice are therefore a great tool with which we can investigate the role of the CaMKII and NMDAR association in chronic pain. If we find that impaired CaMKII association with the NMDAR interferes with chronic pain, then we will move forward with the development of organic agents that interfere with CaMKII binding to the NMDAR as novel therapeutics for the treatment of chronic pain.

Award(s)

  • Recipient, Kirschstein NRSA Individual Predoctoral Fellowship, 2011-present
  • Graduate Incentive Fellowship, University of Iowa Graduate College, 2011
  • Graduate Student Senate Travel Award, 2009
  • Tephly Travel Award, Univesity of Iowa, 2009
  • NIH T32 Pharmacological Sciences Training Grant, University of Iowa, 2008-2010

Research