Patterning of developing embryos requires signaling via different molecules in spacio-temporally regulated manner. Hedgehog is one such highly conserved signaling protein required for embryonic patterning and is also hyper-activated in several cancers. Mechanism of Hedgehog release, transport and reception to activate different target genes for tissue patterning and cancer progression involves intricate processes at molecular and cellular levels. Several evidences including our previous work suggest that Hedgehog proteins are secreted on exovesicles. We find that Hedgehog proteins are secreted on at least two types of exovesicles with distinct proteins and miRNAs. Apart from exovesicles, there are other reported extracellular forms of Hedgehog proteins. However, currently the need for secretion of Hedgehog in different extracellular forms remains unclear.
Our group is interested in probing the basic biology of exovesicular release of Hedgehog and miRNA packaging. Using chick embryos as our model for tissue patterning and leukemia as our disease model, our lab is investigating if different extracellular forms of Hedgehog proteins have distinct functional abilities. In the field of cancer biology our team works closely with practising clinicians to evaluate molecular mechanisms of therapy resistance and cancer progression.
Ganesan S, Kumar Palani H, Lakshmanan V, Balasundaram N, Alex AA, David S, Venkatraman A, Kulkarni UP, George B, Srivastava A, Balasubramanian P, Datta KK, Gowda H, Palakodeti D, Vyas N,* Mathews V.* Stromal-cells down-regulate miR-23a-5p to activate protective autophagy in acute myeloid leukemia. Cell Death Dis. 2019 Sep 30;10(10):736. (*Corresponding author)
Parchure A, Vyas N, Mayor S (2017). Wnt and Hedgehog: Secretion of Lipid-Modified Morphogens. Trends Cell Biol. Online 10 November 2017, doi: 10.1016/j.tcb.2017.10.003.
Vyas N* and Dhawan J (2017). Exosomes: mobile platforms for targeted and synergistic signaling across cell boundaries. Cell Mol Life Sci. 74(9):1567-1576. (*Corresponding author)
Parchure A, Vyas N, Ferguson C, Parton RG, Mayor S (2015). Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion. Mol Biol Cell. 26(25):4700-4717.
Vyas N*, Walvekar A, Tate D, Lakshmanan V, Bansal D, Cicero AL, Raposo G, Palakodeti D, and Dhawan J (2014). Vertebrate Hedgehog is secreted on two types of extracellular vesicles with different signaling properties. Sci Rep. 4:7357. (*Corresponding author)
Vyas N, Goswami D, Manonmani A, Sharma P, Ranganath HA, VijayRaghavan K, Shashidhara LS, Sowdhamini R, Mayor S (2008). Nanoscale organization of Hh is essential for long range signaling. Cell. 133(7):1214-1227. (Also see preview: Vincent JP. Hedgehog nanopackages ready for dispatch. Cell. 133(7):1139-41).
Conference Paper: Ganesan S, Kumar Palani H, Lakshmanan V, Balasundaram N, Alex AA, David S, Venkatraman A, Kulkarni UP, George B, Srivastava A, Balasubramanian P, Datta KK, Gowda H, Palakodeti D, Vyas N and Mathews V (2017). Stromal-Cells Downregulate miR-23a-5p Levels in Myeloid Leukemic Cells to Activate Protective-Autophagy Against Chemotherapeutic Agents. Blood. 130:3780 LP-3780.
Conference Paper: Ganesan S, Lakshmanan V, Palani HK, Balasundaram N, Alex AA, David S, Korula A, George B, Balasubramanian P, Gowda H, Vyas N, Palakodeti D and Mathews V (2016). Role of miRNA in Micro-Environment Mediated Drug Resistance in Acute Promyelocytic Leukemia to Arsenic Trioxide. Blood. 128:5125 LP-5125.
Conference Paper: Ganesan S, Palani HK, Lakshmanan V, Balasundaram N, Alex AA, David S, George B, Balasubramanian P, Vyas, N, Palakodeti D, et al. (2016). Osteoblast Differentiation of Stromal Cells Induced By Leukemic Cells. Blood. 128, 5062 LP-5062.
Anusha, HamzaDalal, Sitalakshmi Subramanian, Snijesh VP, Divya. Gowda, Krishnamurthy H., Sharat Damodar and Neha Vyas. (2021). Exovesicular-Shh confers Imatinib resistance by upregulating Bcl2 expression in chronic myeloid leukemia with variant chromosomes. Cell Death & Disease, 12(259).