Osteoarthritis (OA) is one of the most common forms of joint disease in which the articular cartilage at the end of bone wears down and can no longer fully cushion the interacting bones during movement. OA is accompanied by the formation of osteophytes, causing additional joint pain. There is currently no disease-modifying drug for OA therapy. Crosstalk between the transforming growth factor beta (TGFb) and the bone morphogenic protein (BMP) signaling pathways is essential for the maintenance of healthy bone and cartilage. It has been found that the major role of the TGFb type I receptor (ALK5) in growth plate cartilage is to suppress BMP pathway because the loss of ALK5 leads to formation of ALK1/ActRIIB complexes, leading an increase level of pSmad1/5 mediated BMP signaling. Our initial studies indicate a similar mechanism in articular cartilage. We found that by inhibiting ALK1/2 by either blocking kinase function through BMP-kinase inhibitor (BMP-KI) or by blocking ligand binding through ALK1-Fc, we can prevent the development of post-traumatic osteoarthritis. Micro-CT Analysis and histological analysis using the Osteoarthritis Research Society International (OARSI) semi-quantitative scoring method showed that mice induced with post-traumatic osteoarthritis (PTOA) has significantly less osteophyte volume and articular cartilage damage when treated with the ALK1-Fc or the ALK1-KI. These findings suggest that both ALK1-Fc and BMP-KI are promising therapeutic agents for treating OA, as they both improve the morphology of the joint caused by the disease.

Carbon nanodots (CNDs) are an emerging class of nanomaterials with unique optical, electrical and chemical properties, offering excellent stability, photoluminescence, and easy surface modification. Due to these characteristics, the integration of carbon nanodots into the fabrication of electrodes in electric double-layer capacitors (EDLCs) are of increasing interest. In this approach, a CO2-laser assisted process was utilized to convert CNDs into highly conductive 3D-carbon monoliths, with these laser-reduced carbon nanodots (lrCND) then serving as electrodes for electrochemical capacitors. Laser-reducing halogen doped carbon nanodots enabled the combination of graphene-type sp2 layers with tetrahedral carbon–carbon bonds and nitrogen (pyridinic and pyrrolic) superdoping (16%). The substitution of argon for oxygen in the CO2 laser reaction environment had a positive effect on device parameters and frequency response, and the oxygen-free environment demonstrated a more effective conversion of CNDs into graphitic carbon. The resulting graphitic carbon boasted high specific surface areas and electrical conductivity, and when incorporated into EDLCs, a RC time constant of 0.29 ms and a capacitance of 0.259 mF cm−2 at 120 Hz were obtained.

Toxoplasma gondii is an obligate intracellular parasite that infects nearly one-third of the human population, making it one of the most common parasites in the world. Its intracellular lifecycle is mediated by a series of unique organelles that play roles in motility, invasion, host-cell manipulation and parasite replication. Many of the proteins that target these organelles use the secretory pathway, but precisely how organellar sorting is achieved remains enigmatic. One major organelle that is integral to the parasite’s secretory pathway is the Golgi. Building on our previous in vivo biotinylation (BioID) experiments of the Golgi, we identify here a series of Tre2–Bub2–Cdc16 (TBC)-domain containing proteins, which are involved in in vesicle fusion and intracellular trafficking between the ER-Golgi-Plasma Membrane. In this study, we localize all TBC-domain containing proteins in T. gondii to discrete regions of the secretory pathway. We then use an auxin-inducible degron (AID) gene knockdown approach to demonstrate that a TBC-domain ER protein is essential for parasite survival. This essential gene consists of a conserved ‘dual finger’ active site in the TBC-domain of the protein that is critical for GAP catalytic function. Together these studies provide new insight into intracellular vesicle trafficking in T. gondii and identify putative targets for the design of novel therapeutics that can specifically target the parasite.

The parasite Trypanosoma brucei depends on its flagellum for motility, which is directly required for transmission and pathogenesis. The doublet microtubules at the core of the flagellum contain recently-discovered microtubule inner proteins (MIPs), including a subset of MIPs that comprise the inner junction (IJ) of the doublet. Based on studies of MIPs in other organisms, we hypothesize that MIPs are important for flagellum stability and motility in T. brucei and that T. brucei-specific MIPs contribute to the parasite’s unique motility. There are five known IJ MIPs in T. brucei based on homology to Chlamydomonas, and knockdown of one of these MIPs (FAP106) showed that FAP106 is critical for assembly of other IJ MIPs and novel T. brucei-specific MIP candidates (MCs). At Hill Lab, we are using RNA interference to knockdown individual MIPs and tandem mass tag (TMT) proteomics to identify MIPs lost from the flagellum in each knockdown. Further, functional studies such as motility assays and immunofluorescence assays are conducted on knockdown cell lines to test for phenotypic defects. My studies revealed that MC15 knockdown parasites have a motility defect, and TMT proteomics data showed that MC15 is the only protein lost in its knockdown. This indicates that MC15 is required for motility. I will conduct similar studies of the other four IJ MIPs. These approaches will allow us to study the functions of the IJ MIPs and MCs and determine interdependencies between them, including a mechanism for assembly of the IJ.