Kshitij Parag-Sharma

University of North Carolina at Chapel Hill | UNC · Department of Cell Biology and Physiology

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and incidence rates are continuing to rise globally. Patients often present with locally advanced disease and a staggering 50% chance of relapse following treatment. Aberrant activation of adaptive response signaling pathways, such as the cAMP/PKA pathway, induce...

Bioluminescence imaging with luciferase–luciferin pairs is a well-established technique for visualizing biological processes across tissues and whole organisms. Applications at the microscale, by contrast, have been hindered by a lack of detection platforms and easily resolved probes. We addressed this limitation by combining bioluminescence with p...

Lysyl hydroxylase 2 (LH2) is a member of LH family that catalyzes the hydroxylation of lysine (Lys) residues on collagen, and this particular isozyme has been implicated in various diseases. While its function as a telopeptidyl LH is generally accepted, several fundamental questions remain unanswered: 1, Does LH2 catalyze the hydroxylation of all t...

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and incidence rates are continuing to rise globally. HNSCC patient prognosis is closely related to the occurrence of tumor metastases, and collagen within the tumor microenvironment (TME) plays a key role in this process. Lysyl hydroxylase 2 (LH2), encoded by the...

Objectives Mucoepidermoid carcinoma (MEC) is the most common type of salivary gland malignancy. Advanced or high-grade MECs are refractory to chemotherapy, often leading to tumor recurrence/metastasis and abysmal ~35% 5-year survival. Causal links have been established between Epithelial Growth Factor Receptor (EGFR) activation and poor outcome. He...

Bioluminescent imaging (BLI) has emerged as a popular in vivo tracking modality in bone regeneration studies stemming from its clear advantages: non-invasive, real-time, and inexpensive. We recently adopted bioluminescence resonance energy transfer (BRET) principle to improve BLI cell tracking and generated the brightest bioluminescent signal known...

Mucoepidermoid carcinoma (MEC) is a life-threatening salivary gland cancer that is driven primarily by a transcriptional coactivator fusion composed of cyclic AMP-regulated transcriptional coactivator 1 (CRTC1) and mastermind-like 2 (MAML2). The mechanisms by which the chimeric CRTC1/MAML2 (C1/M2) oncoprotein rewires gene expression programs that p...

Heterotrimeric G-proteins are signal transducers involved in mediating the action of many natural extracellular stimuli as well as of many therapeutic agents. Non-invasive approaches to manipulate the activity of G-proteins with high precision are crucial to understand their regulation in space and time. Here, we developed LOV2GIVe, an engineered m...

Heterotrimeric G-proteins are signal transducers involved in mediating the action of many natural extracellular stimuli and many therapeutic agents. Non-invasive approaches to manipulate the activity of G-proteins with high precision are crucial to understand their regulation in space and time. Here, we developed LOV2GIVe, an engineered modular pro...

Heterotrimeric G-proteins are signal transducers involved in mediating the action of many natural extracellular stimuli and many therapeutic agents. Non-invasive approaches to manipulate the activity of G-proteins with high precision are crucial to understand their regulation in space and time. Here, we developed LOV2GIVe, an engineered modular pro...

Heterotrimeric G-proteins are signal transducers that mediate the action of many natural extracellular stimuli as well as of many therapeutic agents. Non-invasive approaches to manipulate the activity of G-proteins with high precision are crucial to understand their regulation in space and time. Here, we engineered LOV2GIVe, a modular protein that...

p> Introduction: The presence of the t(11;19) chromosomal translocation and its CRTC1-MAML2 (C1/M2) fusion product occurs frequently in salivary mucoepidermoid carcinoma (MEC) and has been correlated with a favorable prognosis. Recently, whole-exome sequencing studies found genomic alterations in MEC to be infrequent, which supports the role of C1/...

Mucoepidermoid carcinoma (MEC) is a life-threatening salivary gland cancer that is driven primarily by the transcriptional co-activator fusion CRTC1-MAML2. The mechanisms by which the chimeric CRTC1-MAML2 oncoprotein rewires gene expression programs that promote tumorigenesis remain poorly understood. Here, we show that CRTC1-MAML2 induces transcri...

Light-inducible optogenetic systems offer precise spatiotemporal control over a myriad of biologic processes. Unfortunately, current systems are inherently limited by their dependence on external light sources for their activation. Further, the utility of Laser/LED-based illumination strategies are often constrained by the need for invasive surgica...

The incidence of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is increasing and implicated in more than 60% of all oropharyngeal carcinomas (OPSCCs). Although whole-genome, transcriptome, and proteome analyses have identified altered signaling pathways in HPV-induced HNSCCs, additional tools are needed to inv...

Mucoepidermoid carcinoma (MEC) is the most common type of malignant salivary gland tumor. MECs frequently exhibit a recurrent t(11;19)(q21;p13) chromosomal translocation that fuses the transcriptional coactivators CRTC1 (CREB-Regulated Transcription Coactivator 1; C1) and MAML2 (Mastermind-Like 2; M2). Though many C1/M2-positive tumors are easily r...

Elucidating receptor occupancy (RO) of monoclonal antibodies (mAbs) is a crucial step in characterizing the therapeutic efficacy of mAbs. However, the in vivo assessment of RO, particularly within peripheral tissues, is greatly limited by current technologies. In the present study, we developed a bioluminescence resonance energy transfer (BRET)-bas...

Objective: The aim of this study was to perform a systematic analysis of the nicotinamide adenine dinucleotide phosphate (NAD[P])-dependent steroid dehydrogenase-like (NSDHL) gene in cases of oral verruciform xanthoma (VX) and to test for the presence of mutations associated with congenital hemidysplasia with ichthyosiform nevus and limb defects (...

Heterotrimeric G proteins are quintessential signalling switches activated by nucleotide exchange on Gα. Although activation is predominantly carried out by G-protein-coupled receptors (GPCRs), non-receptor guanine-nucleotide exchange factors (GEFs) have emerged as critical signalling molecules and therapeutic targets. Here we characterize the mole...

Supplementary figures, supplementary notes and supplementary references.

GIV (aka Girdin) is a Guanine nucleotide Exchange Factor (GEF) that activates heterotrimeric G protein signaling downstream of RTKs and integrins, thereby serving as a platform for signaling cascade crosstalk. GIV is recruited to the cytoplasmic tail of receptors upon stimulation, but the mechanism of activation of its G protein regulatory function...

Auriculo-condylar syndrome (ACS), a rare condition that impairs craniofacial development, is caused by mutations in a G protein-coupled receptor (GPCR) signaling pathway. In mice, disruption of signaling by the endothelin type A receptor (ETAR), which is mediated by the G protein (heterotrimeric guanine nucleotide-binding protein) subunit Gαq/11 an...

Trimeric G protein signaling is a fundamental mechanism of cellular communication in eukaryotes. The core of this mechanism consists of activation of G proteins by the Guanine-nucleotide Exchange Factor (GEF) activity of G protein coupled-receptors (GPCRs). However, the duration and amplitude of G protein-mediated signaling is controlled by a compl...