Sirsi, Shashank R.
Permanent URI for this collectionhttps://hdl.handle.net/10735.1/5910
Shashank Sirsi is an Assistant Professor of Bioengineering. He joined the Erik Jonsson School faculty "to build a state-of-the-art image-guided drug delivery program for cancer therapy." Dr. Sirsi serves as head of the Image-Guided Drug Delivery Lab where his research interests include:
- Cancer,
- Image-guided drug delivery, and
- Ultrasound imaging
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Recent Submissions
Item Impact of Hydrostatic Pressure on Phase-Change Contrast Agent Activation by Pulsed Ultrasound(Acoustical Society of America, 2019-06-14) Raut, Saurabh; Khairalseed, Mawia; Honari, Arvin; Sirsi, Shashank R.; Hoyt, Kenneth; Raut, Saurabh; Khairalseed, Mawia; Honari, Arvin; Sirsi, Shashank R.; Hoyt, KennethA phase-change contrast agent (PCCA) can be activated from a liquid (nanodroplet) state using pulsed ultrasound (US) energy to form a larger highly echogenic microbubble (MB). PCCA activation is dependent on the ambient pressure of the surrounding media, so any increase in hydrostatic pressure demands higher US energies to phase transition. In this paper, the authors explore this basic relationship as a potential direction for noninvasive pressure measurement and foundation of a unique technology the authors are developing termed tumor interstitial pressure estimation using ultrasound (TIPE-US). TIPE-US was developed using a programmable US research scanner. A custom scan sequence interleaved pulsed US transmissions for both PCCA activation and detection. An automated US pressure sweep was applied, and US images were acquired at each increment. Various hydrostatic pressures were applied to PCCA samples. Pressurized samples were imaged using the TIPE-US system. The activation threshold required to convert PCCA from the liquid to gaseous state was recorded for various US and PCCA conditions. Given the relationship between the hydrostatic pressure applied to the PCCA and US energy needed for activation, phase transition can be used as a surrogate of hydrostatic pressure. Consistent with theoretical predictions, the PCCA activation threshold was lowered with increasing sample temperature and by decreasing the frequency of US exposure, but it was not impacted by PCCA concentration. © 2019 Acoustical Society of America.Item Hyposialylated IgG Activates Endothelial IgG Receptor FcγRIIB to Promote Obesity-Induced Insulin Resistance(American Society for Clinical Investigation, 2018-11-05) Tanigaki, K.; Sacharidou, A.; Peng, J.; Chambliss, K. L.; Yuhanna, I. S.; Ghosh, Debabrata; Ahmed, M.; Szalai, A. J.; Vongpatanasin, W.; Mattrey, R. F.; Chen, Q.; Azadi, P.; Lingvay, I.; Botto, M.; Holland, W. L.; Kohler, J. J.; Sirsi, Shashank R.; Hoyt, Kenneth; Shaul, P. W.; Mineo, C.; Ghosh, Debabrata; Sirsi, Shashank R.; Hoyt, KennethType 2 diabetes mellitus (T2DM) is a common complication of obesity. Here, we have shown that activation of the IgG receptor FcγRIIB in endothelium by hyposialylated IgG plays an important role in obesity-induced insulin resistance. Despite becoming obese on a high-fat diet (HFD), mice lacking FcγRIIB globally or selectively in endothelium were protected from insulin resistance as a result of the preservation of insulin delivery to skeletal muscle and resulting maintenance of muscle glucose disposal. IgG transfer in IgG-deficient mice implicated IgG as the pathogenetic ligand for endothelial FcγRIIB in obesity-induced insulin resistance. Moreover, IgG transferred from patients with T2DM but not from metabolically healthy subjects caused insulin resistance in IgG-deficient mice via FcγRIIB, indicating that similar processes may be operative in T2DM in humans. Mechanistically, the activation of FcγRIIB by IgG from obese mice impaired endothelial cell insulin transcytosis in culture and in vivo. These effects were attributed to hyposialylation of the Fc glycan, and IgG from T2DM patients was also hyposialylated. In HFD-fed mice, supplementation with the sialic acid precursor N-acetyl-D-mannosamine restored IgG sialylation and preserved insulin sensitivity without affecting weight gain. Thus, IgG sialylation and endothelial FcγRIIB may represent promising therapeutic targets to sever the link between obesity and T2DM.Item Novel Method for the Formation of Monodisperse Superheated Perfluorocarbon Nanodroplets as Activatable Ultrasound Contrast Agents(Royal Society of Chemistry, 2018-08-20) De, Gracia Lux; Vezeridis, A. M.; Lux, J.; Armstrong, A. M.; Sirsi, Shashank R.; Hoyt, Kenneth; Mattrey, R. F.; Sirsi, Shashank R.; Hoyt, KennethMicrobubble (MB) contrast agents have positively impacted the clinical ultrasound (US) community worldwide. Their use in molecular US imaging applications has been hindered by their limited distribution to the vascular space. Acoustic droplet vaporization (ADV) of nanoscale superheated perfluorocarbon nanodroplets (NDs) demonstrates potential as an extravascular contrast agent that could facilitate US-based molecular theranostic applications. However these agents are metastable and difficult to manufacture with high yields. Here, we report a new formulation technique that yields reliable, narrowly dispersed sub-300 nm decafluorobutane (DFB) or octafluoropropane (OFP)-filled phospholipid-coated NDs that are stable at body temperature, using small volume microfluidization. Final droplet concentration was high for DFB and lower for OFP (>10¹² vs. >10¹⁰ NDs per mL). Superheated ND stability was quantified using tunable resistive pulse sensing (TRPS) and dynamic light scattering (DLS). DFB NDs were stable for at least 2 hours at body temperature (37 °C) without spontaneous vaporization. These NDs are activatable in vitro when exposed to diagnostic US pressures delivered by a clinical system to become visible microbubbles. The DFB NDs were sufficiently stable to allow their processing into functionalized NDs with anti-epithelial cell adhesion molecule (EpCAM) antibodies to target EpCAM positive cells.