HG Wang, Ph.D.Director, Pediatric Molecular Oncology Program
500 University Drive
Hershey, PA 17033
“..we not only need government support, but we also really need
philanthropic support through Four Diamonds to do more and better research to develop new treatment strategies”
R01 GM127954
“Autophagosome closure by the ESCRT machinery”
7/1/2018-3/31/2022
R01 CA222349
“Non-canonical caspase-8 activation on autophagosomal membranes”
8/1/2018-7/31/2023
NIH/NCI P01 CA171983-03
“Targeted Sphingolipid Metabolism for Treatment of AML”
$722,280 (NIH/NCI prime, Subaward from UVA)
Role: MPI – Entire Project; Leader – Project 3; Co-Investigator, Core C and Project 1; MPI – Core E
9/10/2013-8/31/2019
NIH R01 GM117014-01
“TRPM2, Mitochondria, and Cell Survival”
$198,000
Role: Co-Investigator, 2% effort
5/1/2016-4/30/2020
DoD W81XWH-16-1-0117
“Clinical Significance and Mechanistic Insights into Ovarian Cancer Mitochondrial Dysfunction”
$306,306
Role: Co-Investigator, 1% effort
5/1/2016-4/30/2018
NIH R01 CA098472
“Survival Mechanisms in Leukemic NK Cells”
$12,387 (NIH prime / Subaward from UVA)
Role: Consortium P.I., 5% effort
10/1/2013-4/30/2017
NIH/NCI R01 CA082197-16
“Apoptosis Mechanisms and Human Cancer”
$161,191
Role: P.I., 16% effort
6/1/2011-3/31/2017
Hyundai Hope on Wheels
“Switching autophagy to apoptosis for therapeutic benefit in pediatric acute myeloid leukemia”
$125,000
Role: P.I., 10% effort
12/31/2014-12/31/2016
NIH/NCI R21 CA171501-02
“Targeting autophagy in the TME”
$122,670
Role: P.I., 10% effort
7/1/2012-6/30/2015
Dr. Wang is a nationally and internationally recognized scientist. His laboratory is focused on understanding the interplay of autophagy (self-eating) and apoptosis (self-killing) in the context of tumorigenesis and drug resistance.
Targeting these two closely related but distinct self-destructive processes for anticancer drug discovery and development is a major interest of his research group. Dr. Wang has been instrumental in contributing to our knowledge of apoptosis and autophagy.
The body of his scientific work (encompassing a total of 140 articles) has been cited more than 28,000 times with an h-index of 64 (Google Scholar Citations). This speaks to his long-lasting and important impact on the cell biology community.
The following are publications of Dr. Wang’s lab since 2012:
Liu Z, Wei Y, Zhang L, Yee PP, Johnson M, Zhang X, Gulley M, Atkinson JM, Trebak M, Wang HG, Li W. Induction of store-operated calcium entry (SOCE) suppresses glioblastoma growth by inhibiting the Hippo pathway transcriptional coactivators YAP/TAZ. Oncogene 38(1): 120-139, 2019
Dower CM, Bhat N, Gebru MT, Chen L, Wills CA, Miller BA, Wang HG. Targeted Inhibition of ULK1 Promotes Apoptosis and Suppresses Tumor Growth and Metastasis in Neuroblastoma. Mol. Cancer Ther. 17(11): 2365-2376, 2018.
Clements KE, Thakar T, Nicolae CM, Liang X, Wang HG, Moldovan GL. Loss of E2F7 confers resistance to poly-ADP-ribose polymerase (PARP) inhibitors in BRCA2-deficient cells. Nucleic Acids Res. 46(17): 8898-8907, 2018.
Takahashi Y, He H, Tang Z, Hattori T, Liu Y, Young MM, Serfass JM, Chen L, Gebru M, Chen C, Wills CA, Atkinson JM, Chen H, Abraham T, Wang HG. An autophagy assay reveals the ESCRT-III component CHMP2A as a regulator of phagophore closure. Nat. Commun. 9(1): 2855, 2018.
Lima S, Takabe K, Newton J, Saurabh K, Young MM, Leopoldino AM, Hait NC, Roberts JL, Wang HG, Dent P, Milstien S, Booth L, Spiegel S. TP53 is required for BECN1- and ATG5-dependent cell death induced by sphingosine kinase 1 inhibition. Autophagy. 14(6):942-957, 2018.
Hengst JA, Dick TE, Sharma A, Doi K, Hegde S, Tan SF, Geffert LM, Fox TE, Sharma AK, Desai D, Amin S, Kester M, Loughran TP, Paulson RF, Claxton DF, Wang HG, Yun JK. SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models. Cancer Transl. Med. 3(4): 109-121, 2017.
Tang Z, Takahashi Y, Chen C, Liu Y, He H, Tsotakos N, Serfass JM, Gebru MT, Chen H, Young MM, Wang HG. Atg2A/B deficiency switches cytoprotective autophagy to non-canonical caspase-8 activation and apoptosis. Cell Death Differ. 24(12): 2127-2138, 2017.
Fino KK, Yang L, Silveyra P, Hu S, Umstead TM, DiAngelo S, Halstead ES, Cooper TK, Abraham T, Takahashi Y, Zhou Z, Wang HG*, Chroneos ZC*. SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection. Sci. Rep. 7(1): 7262, 2017. *Corresponding authors
Teye EK, Sido A, Xin P, Finnberg NK, Gokare P, Kawasawa YI, Salzberg AC, Shimko S, Bayerl M, Ehmann WC, Claxton DF, Rybka WB, Drabick JJ, Wang HG, Abraham T, El-Deiry WS, Brodsky RA, J Hohl R, Pu JJ. PIGN gene expression aberration is associated with genomic instability and leukemic progression in acute myeloid leukemia with myelodysplastic features. Oncotarget 8(18): 29887-29905, 2017.
Serfass JM, Takahashi Y, Zhou Z, Kawasawa YI, Liu Y, Tsotakos N, Young MM, Tang Z, Yang L, Atkinson JM, Chroneos ZC, Wang HG. Endophilin B2 facilitates endosome maturation in response to growth factor stimulation, autophagy induction, and influenza A virus infection. J. Biol. Chem. 292(24): 10097-10111, 2017.
Zhang C, Liu F, Chen H, Li N, Luo Z, Guo W, Huang D, Tang S, Wang HG, Cheng S, Li Z, Wang H. Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity. Clin. Exp. Metastasis. 34(1): 11-23, 2017.
Teye EK, Sido A, Xin P, Finnberg NK, Gokare P, Kawasawa YI, Salzberg AC, Shimko S, Bayerl M, Ehmann WC, Claxton DF, Rybka WB, Drabick JJ, Wang HG, Abraham T, El-Deiry WS, Brodsky RA, Hohl RJ, Pu JJ. PIGN gene expression aberration is associated with genomic instability and leukemic progression in acute myeloid leukemia with myelodysplastic features. Oncotarget. 2017
Dower CM, Bhat N, Wang EW, Wang HG. Selective Reversible Inhibition of Autophagy in Hypoxic Breast Cancer Cells Promotes Pulmonary Metastasis. Cancer Res. 77(3): 646-657, 2017.
Young MM, Takahashi Y, Fox TE, Yun JK, Kester M, Wang HG. Sphingosine Kinase 1 Cooperates with Autophagy to Maintain Endocytic Membrane Trafficking. Cell Rep. 17(6): 1532-1545, 2016.
Bao L, Chen SJ, Conrad K, Keefer K, Abraham T, Lee JP, Wang J, Zhang XQ, Hirschler-Laszkiewicz I, Wang HG, Dovat S, Gans B, Madesh M, Cheung JY, Miller BA. Depletion of the Human Ion Channel TRPM2 in Neuroblastoma Demonstrates Its Key Role in Cell Survival through Modulation of Mitochondrial Reactive Oxygen Species and Bioenergetics. J. Biol. Chem. 291(47): 24449-24464, 2016.
Liu Q, Chen L, Atkinson JM, Claxton D, Wang HG. Atg5-dependent autophagy contributesto the development of acute myeloid leukemia in an MLL-AF9-driven mouse model. Cell Death Dis. 7(9): e2361, 2016.
Takahashi Y, Tsotakos N, Liu Y, Young M, Serfass J, Tang Z, Abraham T, Wang HG. TheBif-1-Dynamin 2 membrane fission machinery regulates Atg9-containing vesicle generation at the Rab11-positive reservoirs. Oncotarget 7(15): 20855-68, 2016.
Liu Y, Takahashi Y, Desai N, Zhang J, Serfass JM, Shi YG, Lynch CJ, Wang HG. Bif-1 deficiency impairs lipid homeostasis and causes obesity accompanied by insulin resistance. Sci. Rep. 6: 20453, 2016.
Tan SF, Liu X, Fox TE, Barth BM, Sharma A, Turner SD, Awwad A, Dewey A, Doi K, Spitzer B, Shah MV, Morad SA, Desai D, Amin S, Zhu J, Liao J, Yun J, Kester M, Claxton DF, Wang HG, Cabot MC, Schuchman EH, Levine RL, Feith DJ, Loughran TP Jr. Acid ceramidase is upregulated in AML and represents a novel therapeutic target. Oncotarget. 7(50): 83208-83222, 2016.
Niu G, Zhang H, Liu D, Chen L, Belani C, Wang HG, Cheng H. Tid1, the Mammalian Homologue of Drosophila Tumor Suppressor Tid56, Mediates Macroautophagy by Interacting with Beclin1-containing Autophagy Protein Complex. J. Biol. Chem. 290(29): 18102-10, 2015.
Varadarajan S, Poornima P, Milani M, Gowda K, Amin S, Wang HG, Cohen GM. Maritoclax and dinaciclib inhibit MCL-1 activity and induce apoptosis in both a MCL-1-dependent and -independent manner. Oncotarget 6(14): 12668-81, 2015.
Wang DB, Kinoshita Y, Kinoshita C, Uo T, Sopher BL, Cudaback E, Keene CD, Bilousova T, Gylys K, Case A, Jayadev S, Wang HG, Garden GA, Morrison RS. Loss of endophilin-B1 exacerbates Alzheimer’s disease pathology. Brain 138(Pt 7): 2005-19, 2015.
Hsu P, Liu X, Zhang J, Wang HG, Ye JM, Shi Y. Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy. Autophagy 11(4): 643-52, 2015.
Ren T, Takahashi Y, Liu X, Loughran TP, Sun SC, Wang HG, Cheng H. HTLV-1 Tax deregulates autophagy by recruiting autophagic molecules into lipid raft microdomains. Oncogene 34(3):334-45, 2015.
Dick TE, Hengst JA, Fox TE, Colledge AL, Kale VP, Sung SS, Sharma A, Amin S, Loughran TP Jr, Kester M, Wang HG, Yun JK. The apoptotic mechanism of action of the sphingosine kinase 1 selective inhibitor SKI-178 in human acute myeloid leukemia cell lines. J Pharmacol Exp Ther. 352(3): 494-508, 2015.
Sun X, Hasanali ZS, Chen A, Zhang D, Liu X, Wang HG, Feith DJ, Loughran TP Jr, Xu K. Suberoylanilide hydroxamic acid (SAHA) and cladribine synergistically induce apoptosis in NK-LGL leukaemia. Br J Haematol. 168(3):371-83, 2015.
Chen SJ, Hoffman NE, Shanmughapriya S, Bao L, Keefer K, Conrad K, Merali S, Takahashi Y, Abraham T, Hirschler-Laszkiewicz I, Wang J, Zhang XQ, Song J, Barrero C, Shi Y, Kawasawa YI, Bayerl M, Sun T, Barbour M, Wang HG, Madesh M, Cheung JY, Miller BA. A Splice Variant of the Human Ion Channel TRPM2 Modulates Neuroblastoma Tumor Growth Through HIF-1/2α. J Biol Chem. 289(52):36284-302, 2014.
Doi K, Gowda K, Liu Q, Lin JM, Sung SS, Dower C, Claxton D, Loughran TP Jr, Amin S, Wang HG. Pyoluteorin derivatives induce Mcl-1 degradation and apoptosis in hematological cancer cells. Cancer Biol Ther. 15(12):1688-99, 2014
Muppidi A, Doi K, Ramil CP, Wang HG, Lin Q. Synthesis of cell-permeable stapled BH3 peptide-based Mcl-1 inhibitors containing simple aryl and vinylaryl cross-linkers. Tetrahedron 70(42): 7740-7745, 2014.
Doi K, Liu Q, Gowda K, Barth BM, Claxton D, Amin S, Loughran TP Jr, Wang HG. Maritoclax induces apoptosis in acute myeloid leukemia cells with elevated Mcl-1 expression. Cancer Biol Ther. 15(8): 1077-86, 2014.
Wang DB, Uo T, Kinoshita C, Sopher BL, Lee RJ, Murphy SP, Kinoshita Y, Garden GA, Wang HG, Morrison RS. Bax interacting factor-1 promotes survival and mitochondrial elongation in neurons. J Neurosci. 34(7): 2674-83, 2014.
Muppidi A, Doi K, Edwardraja S, Pulavarti SV, Szyperski T, Wang HG, Lin Q. Targeted delivery of ubiquitin-conjugated BH3 peptide-based Mcl-1 inhibitors into cancer cells. Bioconjug Chem. 25(2): 424-32, 2014.
Young M, Kester M, Wang HG. Sphingolipids: regulators of crosstalk between apoptosis and autophagy. J. Lipid Res. 54: 5-19, 2013.
Ryland LK, Doshi UA, Shanmugavelandy SS, Fox TE, Aliaga C, Broeg K, Baab KT, Young M, Khan O, Haakenson JK, Jarbadan NR, Liao J, Wang HG, Feith DJ, Loughran TP Jr, Liu X, Kester M. C6-ceramide nanoliposomes target the warburg effect in chronic lymphocytic leukemia. PLoS One 8(12): e84648, 2013.
Pandey MK, Gowda K, Doi K, Sharma AK, Wang HG, Amin S. Proteasomal degradation of Mcl-1 by maritoclax induces apoptosis and enhances the efficacy of ABT-737 in melanoma cells. PLoS One 8(11): e78570, 2013.
He S, Ni D, Ma B, Lee JH, Zhang T, Ghozalli I, Pirooz SD, Zhao Z, Bharatham N, Li B, Oh S, Lee WH, Takahashi Y, Wang HG, Minassian A, Feng P, Deretic V, Pepperkok R, Tagaya M, Yoon HS, Liang C. PI(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the Beclin1 complex. Nat Cell Biol. 15(10): 1206-19, 2013.
Yang Y, Fiskus W, Yong B, Atadja P, Takahashi Y, Pandita TK, Wang HG, Bhalla KN. Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy. Proc Natl Acad Sci U S A. 110(17): 6841-6, 2013.
Takahashi Y, Hori T, Cooper TK, Liao J, Desai N, Serfass JM, Young MM, Park S, Izu Y, Wang HG. Bif-1 haploinsufficiency promotes chromosomal instability and accelerates Myc-driven lymphomagenesis via suppression of mitophagy. Blood 121: 1622-32, 2013.
Takahashi Y, Young MM, Serfass JM, Hori T, Wang HG. Sh3glb1/Bif-1 and mitophagy: Acquisition of apoptosis resistance during Myc-driven lymphomagenesis. Autophagy 29: 9(7), 2013.
Young M, Wang HG. The crosstalk between apoptosis and autophagy. In: Autophagy and Cancer. Wang HG (editor), Springer, 2013.
Takahashi Y, Young MM, Wang HG. SNAPping off Golgi membranes for autophagosome formation. Cell Cycle 12(1): 15-6, 2013.
Ding W, Dang H, You H, Steinway S, Takahashi Y, Wang HG, Liao J, Stiles B, Albert R, Rountree CB. miR-200b restoration and DNA methyltransferase inhibitor block lung metastasis of mesenchymal-phenotype hepatocellular carcinoma. Oncogenesis 2012 Jun 11;1:e15.
Muppidi A, Doi K, Edwardraja S, Drake EJ, Gulick AM, Wang HG, Lin Q. Rational design of proteolytically stable, cell-permeable Peptide-based selective mcl-1 inhibitors. J Am Chem Soc. 134: 14734-7, 2012.
Ren T, Dong W, Takahashi Y, Xiang D, Yuan Y, Liu X, Loughran TP, Sun SC, Wang HG, Cheng H. HTLV-2 Tax immortalizes human CD4+ memory T lymphocytes by oncogenic activation and dysregulation of autophagy. J Biol Chem. 287: 34683-93, 2012.
Kim YB, Balasis ME, Doi K, Berndt N, DuBoulay C, Hu C, Guida W, Wang HG, Sebti SM, Del Vallea JR. Synthesis and evaluation of substituted hexahydronaphthalenes as novel inhibitors of the Mcl-1/BimBH3 interaction. Bioorg Med Chem Lett. 22: 5961-5, 2012.
Zhang Y, Cheng Y, Ren X, Hori T, J Huber-Keener K, Zhang L, Yap KL, Liu D, Shantz LM, Qin ZH, Zhang S, Wang J, Wang HG, Shih IM, Yang JM. Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis. Cancer Res. 72: 4262-75, 2012.
Runkle KB, Meyerkord CL, Desai NV, Takahashi Y, Wang HG. Bif-1 suppresses breast cancer cell migration by promoting EGFR endocytic degradation. Cancer Biol. Ther. 13: 956-966, 2012.
Young M, Takahashi Y, Khan O, Park S, Hori T, Yun J, Amin S, Hu CD, Zhang J, Kester M, Wang HG. Autophagosomal membrane serves as a platform for an intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. J. Biol. Chem. 287: 12455-68, 2012.
Doi K, Li R, Sung SS, Wu H, Liu Y, Manieri W, Krishnegowda G, Awwad A, Dewey A, Liu X, Amin S, Cheng C, Qin Y, Schonbrunn E, Daughdrill G, Loughran T P, Sebti S, Wang HG. Discovery of Marinopyrrole A (Maritoclax) as a Selective Mcl-1 Antagonist that Overcomes ABT-737 Resistance by Binding to and Targeting Mcl-1 for Proteasomal Degradation. J. Biol. Chem. 287: 10224-35, 2012
