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Grace Laboratory

Peter M. Grace, Ph.D.

Principal Investigator

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Grace Laboratory
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Areas of Research

Pain
Chemotherapy-Induced Neuropathy
Neuron-glial Interactions
Transcriptional Regulation

Chronic pain afflicts 100 million Americans, and therapies that target only neurons are minimally effective. The Grace Lab in MD Anderson's Department of Symptom Research is investigating adaptive immune mechanisms that initiate and maintain neuropathic pain after traumatic nerve injury. The lab is also delineating the analgesic mechanisms and therapeutic potential of the "master regulator" of the antioxidant response Nrf2. Because recent research has shown that the Nrf2 activator dimethyl fumarate relieves neuropathic pain, ongoing efforts are focused on advancing this drug class for the clinical treatment of chronic pain.

Our Research Goal

The overall goal of the Grace Lab is to discover the adaptive immune mechanisms that initiate and maintain neuropathic pain after nerve injury.

Current Research

The Antioxidant Transcription Factor Nrf2: A New Therapeutic Target for Neuropathic Pain

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Funding: The US National Institues of Health (grant # 1RF1NS113840: Nrf2 Activation for Addiction-Free Treatment of Neuropathic Pain)

In rodent models of pain, reactive oxygen and nitrogen species are elevated in neuronal, immune, and glial cells in the dorsal root ganglia and spinal cord dorsal horn.

Reactive oxygen and nitrogen species promote hyperexcitability of neurons in pain pathways via several mechanisms (summarized in Figure 1), including:

Direct activation of nociceptors via transient receptor potential (TRP) channels.
Impairment of mitochondrial function, which is believed to contribute to spontaneous nociceptor activity.
Activation of signaling cascades that produce proinflammatory mediators that increase the excitability of neurons in the pain neuraxis.

This project tests whether activating the antioxidant transcription factor Nrf2 will restore redox balance to simultaneously resolve multiple mechanisms that are implicated as drivers of neuropathic pain. To this end, we have:

Used genetic and pharmacological approaches to modulate Nrf2 activity in mouse models of neuropathic pain.
Used biochemistry, microscopy, and live-cell imaging techniques to investigate the molecular and cellular consequences of Nrf2 activation in both mouse and human tissues.

The insights gained from these investigations may lead to novel mechanism-based therapeutics for pain.

Fc Gamma Receptor Signaling: A New Pathway for Sustained Neuropathic Pain

Funding: The Rita Allen Foundation and the US Department of Defense (grant # W81XWH19-1-0160: Fc Gamma Receptor Signaling: A New Pathway for Sustained Neuropathic Pain)

Spinal cord glia activated after peripheral nerve injury release proinflammatory mediators that promote neuronal hyperexcitability within pain pathways.

Although the signals that trigger microglial reactivity after peripheral nerve injury have been closely studied, those that maintain astrocyte reactivity and prevent pain resolution are not well understood.
We have evidence to suggest that sustained mediator production by astrocytes is facilitated by activation of FcgR subtype IIa (FcγRIIa) via autoimmune complexes. These receptors are uniquely expressed by astrocytes after peripheral nerve injury (Figure 2).

This project aims to delineate the mechanisms of FcgRIIa signaling after peripheral nerve injury and to identify the autoantigens involved.

Grace Lab - Fc gamma receptor signaling

News and Accolades

Jiahe Li’s 2020 article in Anesthesiology has been covered by the Pain Research Forum. Her work shows that the MS drug dimethyl fumarate has therapeutic effects in a rodent model of neuropathic pain.

Join Our Lab

We highly value hard work, curiosity, innovation, teamwork and professional development in combination with a healthy work/life balance. We seek strong postdoctoral fellows to add to our team.