Staff Collaborate Conference Room

Jong-In Park, PhD

Jong-In Park

Jong-In Park, PhD

Professor

Locations

  • Biochemistry
    BSB 357

Contact Information

Biography

Dr. Park earned a PhD in Biochemistry and Molecular Genetics from the University of New South Wales, Sydney, Australia in 2000 for studies in Ras pathway-mediated stress responses.& His postdoctoral training in Cancer Biology was completed at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in 2005. Previously, he earned Bachelor’s and Master’s degrees in Biochemistry from Yonsei University, Seoul, Korea, and worked for the pharmaceutical branch of SAMSUNG, Inc. He joined the faculty of the Biochemistry Department at the Medical College of Wisconsin in 2006.

Dr. Park’s current basic cancer research programs are supported by the NIH-National Cancer Institute and the American Cancer Society (ACS). He also participates in clinical cancer research by serving the NCI-MATCH Precision Medicine Cancer Trial as the Translational Chair of the Dabrafenib & Trametinib combination therapy arm, which targets BRAF-driven cancer. He is currently an ACS Research Scholar and a member of the ACS MEN2 Thyroid Cancer Consortium.

Education

BA and MBioch, Yonsei University, Seoul, Korea
PhD, University of New South Wales, Sydney, Australia, 2000

Research Interests

Proliferative programs of normal mammalian cells are interfaced with a variety of, so called, “innate tumor-suppressive mechanisms” that can trigger growth arrest or cell death in response to aberrant cell proliferation signals such as oncogenic mutations. Therefore, for carcinogenesis to occur, these mechanisms must be inactivated (A model is depicted at right). This inactivation usually requires reprogramming of signaling and metabolic pathways. parksignalingmodelVery intriguingly, certain oncogene-associated tumor suppressive mechanisms can be reactivated in cancer, providing a rationale for the design of a strategy to trigger “synthetic lethality” in cancer. The primary goal of our research is to understand the molecular mechanisms underlying these events and to translate the knowledge into an advanced therapeutic strategy.

Our current research focuses include:

Investigating the role of mortalin/GRP75/HSPA9 in Ras/Raf-transformed cancer. The Ras and Raf families of oncogenes have been known for decades as transforming genes, and activation of the Raf/MEK/ERK pathway is a central signature of many epithelial cancers. However, paradoxically, aberrant activation of Ras or Raf elicits growth inhibitory effects, mainly characterized by cell cycle arrest and senescence, in a variety of cell types and in vivo. These responses are appreciated as innate tumor defense mechanisms against Ras- and Raf-mediated tumorigenesis. We recently demonstrated that mortalin, a mitochondrial molecular chaperone often upregulated in cancers, can determine cell fate in the face of oncogenic Ras/Raf mutations. Importantly, mortalin depletion or inhibition reactivated the tumor suppressive mechanisms associated with Raf/MEK/ERK in cancer cells. Current studies, supported by the NIH/NCI, focus on further elucidating the molecular and biochemical mechanisms underlying mortalin-regulated signaling and metabolic pathways. Moreover, we evaluate therapeutic potential of small molecule inhibitors relevant in this context.

Investigating oncogenic signaling pathways and mitochondrial metabolism in thyroid cancer. Somatic as well as inherited mutations in the RET receptor tyrosine kinase are a key etiological factor for thyroid cancer. Further, inherited RET mutations are an important prognostic marker for the multiple endocrine neoplasia type 2 (MEN2) syndrome, wherein medullary thyroid cancer is a key pathological presentation. As a member of the American Cancer Society MEN2 consortium, we study the underlying molecular and biochemical mechanisms altered in thyroid cancer. We recently demonstrated that metabolic reprogramming in mitochondria is critical for medullary thyroid cancer cell survival and RET expression, thus proposing mitochondria as a potential therapeutic target for this tumor. Our current research further evaluates therapeutic potential of targeting mitochondrial metabolism in thyroid cancer.

Participation in the NCI-MATCH Precision Medicine Cancer Trial. This clinical trial is a “genotype to phenotype” phase II study. An important goal of this study is to identify the features of various tumor types with the same mutation that cause them to either respond to or resist treatment with a targeted therapy. More information is available at the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) Trial Website.

Publications

  • A cellular threshold for active ERK1/2 levels determines Raf/MEK/ERK-mediated growth arrest versus death responses.

    (Hong SK, Wu PK, Park JI.) Cell Signal. 2018 Jan;42:11-20.

  • Steady-State Levels of Phosphorylated Mitogen-Activated Protein Kinase Kinase 1/2 Determined by Mortalin/HSPA9 and Protein Phosphatase 1 Alpha in and Tumor Cells.

    (Wu PK, Hong SK, Park JI.) Mol Cell Biol. 2017 Sep 15;37(18).

  • Vandetanib and cabozantinib potentiate mitochondria-targeted agents to suppress medullary thyroid carcinoma cells.

    (Starenki D, Hong SK, Wu PK, Park JI.) Cancer Biol Ther. 2017 Jul 03;18(7):473-483.

  • Suppression of B-Raf melanoma cell survival by targeting mitochondria using triphenyl-phosphonium-conjugated nitroxide or ubiquinone.

    (Hong SK, Starenki D, Wu PK, Park JI.) Cancer Biol Ther. 2017 02;18(2):106-114.

  • Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).

    (Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, Airoldi EM, Ait-Si-Ali S, Akematsu T, Akporiaye ET, Al-Rubeai M, Albaiceta GM, Albanese C, Albani D, Albert ML, Aldudo J, Algül H, Alirezaei M, Alloza I, Almasan A, Almonte-Beceril M, Alnemri ES, Alonso C, Altan-Bonnet N, Altieri DC, Alvarez S, Alvarez-Erviti L, Alves S, Amadoro G, Amano A, Amantini C, Ambrosio S, Amelio I, Amer AO, Amessou M, Amon A, An Z, Anania FA, Andersen SU, Andley UP, Andreadi CK, Andrieu-Abadie N, Anel A, Ann DK, Anoopkumar-Dukie S, Antonioli M, Aoki H, Apostolova N, Aquila S, Aquilano K, Araki K, Arama E, Aranda A, Araya J, Arcaro A, Arias E, Arimoto H, Ariosa AR, Armstrong JL, Arnould T, Arsov I, Asanuma K, Askanas V, Asselin E, Atarashi R, Atherton SS, Atkin JD, Attardi LD, Auberger P, Auburger G, Aurelian L, Autelli R, Avagliano L, Avantaggiati ML, Avrahami L, Awale S, Azad N, Bachetti T, Backer JM, Bae DH, Bae JS, Bae ON, Bae SH, Baehrecke EH, Baek SH, Baghdiguian S, Bagniewska-Zadworna A, Bai H, Bai J, Bai XY, Bailly Y, Balaji KN, Balduini W, Ballabio A, Balzan R, Banerjee R, Bánhegyi G, Bao H, Barbeau B, Barrachina MD, Barreiro E, Bartel B, Bartolomé A, Bassham DC, Bassi MT, Bast RC Jr, Basu A, Batista MT, Batoko H, Battino M, Bauckman K, Baumgarner BL, Bayer KU, Beale R, Beaulieu JF, Beck GR Jr, Becker C, Beckham JD, Bédard PA, Bednarski PJ, Begley TJ, Behl C, Behrends C, Behrens GM, Behrns KE, Bejarano E, Belaid A, Belleudi F, Bénard G, Berchem G, Bergamaschi D, Bergami M, Berkhout B, Berliocchi L, Bernard A, Bernard M, Bernassola F, Bertolotti A, Bess AS, Besteiro S, Bettuzzi S, Bhalla S, Bhattacharyya S, Bhutia SK, Biagosch C, Bianchi MW, Biard-Piechaczyk M, Billes V, Bincoletto C, Bingol B, Bird SW, Bitoun M, Bjedov I, Blackstone C, Blanc L, Blanco GA, Blomhoff HK, Boada-Romero E, Böckler S, Boes M, Boesze-Battaglia K, Boise LH, Bolino A, Boman A, Bonaldo P, Bordi M, Bosch J, Botana LM, Botti J, Bou G, Bouché M, Bouchecareilh M, Boucher MJ, Boulton ME, Bouret SG, Boya P, Boyer-Guittaut M, Bozhkov PV, Brady N, Braga VM, Brancolini C, Braus GH, Bravo-San Pedro JM, Brennan LA, Bresnick EH, Brest P, Bridges D, Bringer MA, Brini M, Brito GC, Brodin B, Brookes PS, Brown EJ, Brown K, Broxmeyer HE, Bruhat A, Brum PC, Brumell JH, Brunetti-Pierri N, Bryson-Richardson RJ, Buch S, Buchan AM, Budak H, Bulavin DV, Bultman SJ, Bultynck G, Bumbasirevic V, Burelle Y, Burke RE, Burmeister M, Bütikofer P, Caberlotto L, Cadwell K, Cahova M, Cai D, Cai J, Cai Q, Calatayud S, Camougrand N, Campanella M, Campbell GR, Campbell M, Campello S, Candau R, Caniggia I, Cantoni L, Cao L, Caplan AB, Caraglia M, Cardinali C, Cardoso SM, Carew JS, Carleton LA, Carlin CR, Carloni S, Carlsson SR, Carmona-Gutierrez D, Carneiro LA, Carnevali O, Carra S, Carrier A, Carroll B, Casas C, Casas J, Cassinelli G, Castets P, Castro-Obregon S, Cavallini G, Ceccherini I, Cecconi F, Cederbaum AI, Ceña V, Cenci S, Cerella C, Cervia D, Cetrullo S, Chaachouay H, Chae HJ, Chagin AS, Chai CY, Chakrabarti G, Chamilos G, Chan EY, Chan MT, Chandra D, Chandra P, Chang CP, Chang RC, Chang TY, Chatham JC, Chatterjee S, Chauhan S, Che Y, Cheetham ME, Cheluvappa R, Chen CJ, Chen G, Chen GC, Chen G, Chen H, Chen JW, Chen JK, Chen M, Chen M, Chen P, Chen Q, Chen Q, Chen SD, Chen S, Chen SS, Chen W, Chen WJ, Chen WQ, Chen W, Chen X, Chen YH, Chen YG, Chen Y, Chen Y, Chen Y, Chen YJ, Chen YQ, Chen Y, Chen Z, Chen Z, Cheng A, Cheng CH, Cheng H, Cheong H, Cherry S, Chesney J, Cheung CH, Chevet E, Chi HC, Chi SG, Chiacchiera F, Chiang HL, Chiarelli R, Chiariello M, Chieppa M, Chin LS, Chiong M, Chiu GN, Cho DH, Cho SG, Cho WC, Cho YY, Cho YS, Choi AM, Choi EJ, Choi EK, Choi J, Choi ME, Choi SI, Chou TF, Chouaib S, Choubey D, Choubey V, Chow KC, Chowdhury K, Chu CT, Chuang TH, Chun T, Chung H, Chung T, Chung YL, Chwae YJ, Cianfane.) Autophagy. 2016;12(1):1-222.

  • MEK1/2 Inhibitors: Molecular Activity and Resistance Mechanisms.

    (Wu PK, Park JI.) Semin Oncol. 2015 Dec;42(6):849-62.

  • Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo.

    (Starenki D, Park JI.) Endocrinol Metab (Seoul). 2015 Dec;30(4):593-603.

  • ERK1/2 can feedback-regulate cellular MEK1/2 levels.

    (Hong SK, Wu PK, Karkhanis M, Park JI.) Cell Signal. 2015 Oct;27(10):1939-48.

  • Phosphoinositide and Erk signaling pathways mediate activity-driven rodent olfactory sensory neuronal survival and stress mitigation.

    (Kim SY, Mammen A, Yoo SJ, Cho B, Kim EK, Park JI, Moon C, Ronnett GV.) J Neurochem. 2015 Aug;134(3):486-98.

  • Active ERK2 is sufficient to mediate growth arrest and differentiation signaling.

    (Wu PK, Hong SK, Yoon SH, Park JI.) FEBS J. 2015 Mar;282(6):1017-30.

  • Sp1 regulates Raf/MEK/ERK-induced p21(CIP1) transcription in TP53-mutated cancer cells.

    (Karkhanis M, Park JI.) Cell Signal. 2015 Mar;27(3):479-86.

  • Pediatric Medullary Thyroid Carcinoma.

    (Starenki D, Park JI.) J Pediatr Oncol. 2015;3(2):29-37.