This application is for renewal of the T32 comprehensive institutional research-training grantCOSTAR (Craniofacial Oral-Biology Student Training in Academic Research). Building onlongstanding institutional research training experience, COSTAR has trained 26 DDS/PhDstudents, 41 PhD students, 26 Post-doctoral Fellows, 4 faculty fellows, and 147 summer dentalstudent research fellows since first funded in 2002.

Co-abuse of cocaine and alcohol is one of the most common, and dangerous drug pairings, as evidenced bytheir concurrent use being a major cause for emergency hospitalization. Thus, this drug combination is notonly a serious health threat to the individual user, but a major public health burden. Currently, there are noeffective treatments for addiction to cocaine and ethanol, underscoring the vital need to understand themechanistic basis of this highly addictive drug pairing in order to discover new targets for therapeuticintervention.

Role of intracellular membrane signalosomes in B cell NF-kB activationThis proposal focuses on a novel mechanism that underlies NF-kB activation in peripheral B cell differentiationand, when dysregulated in autoreactive B cells, promotes pathogenic autoantibody responses in autoimmunediseases, such as lupus. As we contend, this mechanism is underpinned by the formation of intracellularmembrane signalosomes (IM signalosomes), e.g., as mediated by the interaction of signal adaptor TRAF6, anE3 ubiquitin ligase, with Rab7, an endosome-tethered small GTPase, in B cells upon CD40 engagement.

This renewal application stems from our successful first four years of a Bridge-to-the-Doctorate grant (SouthTexas Doctoral Bridge Program (STDBP; 2013-2017) supporting a partnership between the University ofTexas Health Science Center at San Antonio (UT Health San Antonio; PhD-granting) and Texas StateUniversity ? San Marcos (TxState, master's granting).