Research Interests

Cross-talk between the nervous system and other tissues including organs and immune cells is critical for the regulation of homeostasis as well as the body’s response to trauma, infection, and malignancy. The lab uses a variety of in vitro and in vivo approaches, including anatomical studies, behavior assays, optogenetics, calcium imaging, flow cytometry, immunoassays, and -omics.  Collaborations include working with a variety of expert neuroscientists, statisticians/bioinformaticists, geneticists and immunologists as well as clinical oncologists,, surgeons, and gastroenterologists.

Current Research Interests

1. Neural regulation of tumorigenesis, anti-tumor immunity and cancer pain.

2. Autonomic-sensory circuits that regulate pancreas function, pancreatitis and pancreatic pain syndromes.

3. Identification and validation of diagnostic, predictive, and therapeutic biomarkers for pancreatitis and pancreatic pain syndromes.

4. Peripheral nervous system function and nociception

 

Neural Regulation of Pancreas, Pancreatitis and Pain 

We are interested in understanding the peripheral and central circuitry, involved in regulation of normal pancreas function, development and maintenance of pancreatitis and pancreatic pain. Pancreatitis is a debilitating disease characterized by a high incidence of abdominal pain. We are investigating underlying mechanisms and circuitry using classical animal models as well as a novel optogenetic models. 

Biomarkers for Pancreatitis Progression, Pain and Response to Therapy

Currently, there are no diagnostic biomarkers (behavioral, genomic, or proteomic) for early chronic pancreatitis before irreversible morphological changes occur. Furthermore, we know there are many subtypes of pain within the chronic pancreatitis population, but there are very little data to link specific mechanisms with distinct pain presentations.

Biospecimens, patient reported outcomes (e.g. quantitative sensory testing, pain surveys), and -omics analyses to identify potential biomarkers for both diagnosis of chronic pancreatitis as well as specific subtypes of pain.

Through collaborations with NIDDK/NCI sponsored consortia, we have two clinical trials currently focused  on biopsychosocial predictors of response to endotherapy or total pancreatectomy with islet autotransplant, respectively. 

Human pancreas tumor exhibits close association between intratumoral nerve axons (red) and B  and T lymphocytes, (green and yellow, respectively)

Neuro-immune regulation of the tumor microenvironment

There are several ongoing projects investigating mechanisms associated with this neuroplasticity in animal models and human tumor tissues. Clinically, several tumor types are associated with significant sprouting and hypertrophy of peripheral axons resulting in more innervation than that found in the normal healthy organ. The extent of pain and sensorimotor deficits is associated with penetration of the nerves by tumor and immune cells, a phenomenon called perineural invasion. In a genetic model of pancreas cancer, sensory denervation slows or even prevents tumor growth. Ongoing projects are focused on understanding the mechanisms underlying this phenomenon.

 Given that the tumor microenvironment often has a significant immune infiltration characterized by a suppressive phenotype, we have expanded this line of investigation to understand how peripheral neurons regulate tumor immune profiles.