Basic Science & Translational Research

The Ostlund Lab research focuses on the investigation of neural mechanisms of decision making and motivated behavior, including how chronic drug use impacts the brain to support pathological drug-seeking behavior. A multidisciplinary approach is applied to measure and manipulate the activity of genetically and anatomically targeted neural circuits in rodents performing sophisticated behavioral tasks. Determining how ascending dopamine systems contribute to behavior is a major area of study in the lab. Fast-scan cyclic voltammetry and microdialysis are used to characterize distinct aspects of dopamine signaling to determine their relationship to learning and behavior and how this is altered in addiction and other pathological states. A range of strategies, including chemo and optogenetic tools, are used to selectively perturb the function of dopamine and other neurochemical signaling pathways to determine their specific contributions to behavior.

Principal Investigator: Sean Ostlund, PhD

The Luo Lab research focuses on molecular mechanisms of chronic pain. A multidisciplinary approach is used to study how chronic pain-inducing conditions, such as peripheral nerve injury, spinal cord injury and bone cancer, activate changes in gene expression in sensory pathways that lead to lowered thresholds for spinal neuron activation and pain perception.

Principal Investigator: Zhigang David Luo, MD, PhD

Recent Study

Validation of blocking TSP4/Cava2d1 interaction as a new target for neuropathic pain

Aligned with the NIH Helping to End Addiction Long-term Initiative (NIH HEAL), the research focuses on validating a novel molecular target for nonaddictive neuropathic pain therapeutics. Following nerve injury, coordinated upregulation of CaVα2δ1 and thrombospondin-4 (TSP4) in sensory and spinal neurons was identified as drivers of maladaptive synaptogenesis and spinal sensitization. A critical interaction site on TSP4 has been defined and ongoing studies are investigating whether pharmacologic inhibition or genetic deletion of this site prevents neuropathic pain development in preclinical models. This work aims to advance targeted, mechanism-based strategies for chronic pain treatment.

Selected Publications

• Yanhui Peter Yu, Nian Gong, Tae Dong Kweon, Benjamin Vo, Z David Luo. Gabapentin prevents synaptogenesis between sensory and spinal cord neurons induced by thrombospondin-4 acting on pre-synaptic Cav α2 δ1 subunits and involving T-type Ca2+ channels. Br J Pharmacol. 2018 Jun;175(12):2348-2361. doi: 10.1111/bph.14149. Epub 2018 Mar 1. PMID: 29338087

• John Francisco Park, Yanhui Peter Yu, Nian Gong, Van Nancy Trinh, Z David Luo. The EGF-LIKE domain of thrombospondin-4 is a key determinant in the development of pain states due to increased excitatory synaptogenesis. J Biol Chem. 2018 Oct 19;293(42):16453-16463. doi: 10.1074/jbc.RA118.003591. Epub 2018 Sep 7. PMID: 30194282

• Nian Gong, Garo Hagopian, Todd C Holmes, Z David Luo, Xiangmin Xu. Functional Reorganization of Local Circuit Connectivity in Superficial Spinal Dorsal Horn with Neuropathic Pain States. eNeuro. 2019 Oct 10;6(5):ENEURO.0272-19.2019. doi: 10.1523/ENEURO.0272-19.2019. Print 2019 Sep/Oct. PMID: 31533959

• Karina Genaro, Z David Luo. Pathophysiological roles of thrombospondin-4 in disease development. Semin Cell Dev Biol. 2024 Mar 1;155(Pt B):66-73. doi: 10.1016/j.semcdb.2023.06.007. Epub 2023 Jun 28. PMID: 37391348

• Meredith C B Adams, Carla M Bann, Emine Ozgur Bayman, Maria Chao, Georgene W Hergenroeder, Charles Knott, Martin A Lindquist , Z David Luo, Rosemarie Martin, Maryann E Martone, John McCarthy, Micah McCumber, Sharon B Meropol, Ty A Ridenour, Lissette M Saavedra, Abeed Sarker, Kevin J Anstrom, Wesley K Thompson. Building community through data: the value of a researcher driven open science ecosystem. Pain Med. 2025 Jun 1;26(6):295-298. doi: 10.1093/pm/pnaf003. PMID: 39836639

The Alkire Lab research interest focuses on investigating the mechanisms of anesthetic action on learning, memory, consciousness and pain processing. Neuroimaging technologies such as positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG), as well as small animal experimentation, are used to identify and experimentally manipulate various key sites of anesthetic action in the brain.

Principal Investigator: Michael Alkire, MD