Basic Research

Basic Research

Applied Research

Basic Research

Traumatic brain injury (TBI) and many other brain diseases/injuries exhibit sex differences in prevalence. onset. and outcomes. Some of these differences are attributed to the fact that the human brain is sexually dimorphic and there are certain regional and structural differences that exist between male and female brains. However. the effect of these sex variations in biomechanical responses of brain have not been elucidated. The paucity of sex-specific knowledge in brain biomechanics and TBI fields is mainly due to the fact that. these fields have predominantly focused on males.

A2-oxindole forming heme enzyme. MarE. had been proposed as a fifth member pending structural validation.45 MarE is a functionally characterized monooxygenase that generates the oxindole moiety found in the biosynthetic pathways for maremycins (A - G). spirotryprostatin (A - B). and others. We will determine the crystal structure of MarE and revisit its catalytic function.

The external globus pallidus (GPe) is usually considered simply a relay in the indirect pathway between the striatum and the basal ganglia output neurons in the internal pallidal segment and substantia nigra. This view has been disrupted by recent findings that the GPe contains several different cell types. with different striatal afferents that include the direct pathway. and different downstream targets. and which are interconnected in the GPe by their axon collateral arborizations.

The prevalence of neuropsychiatric disorders is increasing. constituting 28% of the global burden of non-communicable disease. A major cause of these disorders is that of aberrant fetal brain development. and there is growing evidence implicating prenatal exposures as a driving factor. A common exposure that has undergone an exponential increase in incidence during recent years is that of viral infections. due in part to the novel coronavirus disease 2019 (COVID-19) pandemic. Up to 80% of hospitalized COVID-19 patients have manifested neurological complications.

The tryptophan degradation pathway is used to prevent unrestrained immune activation in healthy cells. However. tumors hijack this mechanism to escape immune surveillance. The key enzyme of this pathway. tryptophan 2.3-dioxygenase (TDO) and indoleamine 2.3-dioxygenase (IDO). are established immune checkpoint proteins. Tumors enhance their expression to block T cell proliferation and induce T cell death. thereby avoiding immune system surveillance and increasing tumor cell migration capacity. Thus.

Our goal in this highly collaborative project is to develop compounds to selectively activate the delta opioid receptor (DOR)-kappa opioid receptor (KOR) heteromer allosterically. to promote antinociception effects in vivo and advance lead compounds as possible therapies for pain.Our approach will focus on a DOR/KOR heteromer characteristic known as ???interprotomer allosterism???.