Jong-In Park, PhD
PhD, University of New South Wales, Sydney, Australia, 2000
MA, Yonsei University, Seoul, Korea, 1990
BA, Yonsei University, Seoul, Korea, 1988
Dr. Park earned his Bachelor’s and Master’s degrees in Biochemistry and worked for the pharmaceutical branch of SAMSUNG, Inc until he decided to pursue an academic career. Dr. Park received his PhD degree in Biochemistry and Molecular Genetics for studies of Ras-regulated stress responses in yeast. He then conducted postdoctoral research on the role of the MAP kinase pathways for oncogenic Ras, Raf, and receptor tyrosine kinases in human cancer. Upon completing his training, Dr. Park joined the faculty of the Biochemistry Department at the Medical College of Wisconsin in 2006. Since then, Dr. Park has been studying oncogenic signaling and metabolic pathways in different tumors with the support from various funding agencies, including the NIH-National Cancer Institute, the American Cancer Society, and the Department of Defense.
In addition to basic science research, Dr. Park also conducts clinical cancer research. For example, since 2014, he has been participating in the NCI-MATCH Precision Medicine Cancer Trial as the Translational Chair of the Dabrafenib & Trametinib combination therapy arm, which targets BRAF-driven cancer. Dr. Park is a former recipient of the ACS Research Scholar award, the DOD New Investigator award, and the FAMRI Young Investigator award. At MCW, Dr. Park received multiple recognitions as Outstanding Medical Student Teacher and Outstanding Graduate Student Teacher.
- Cell Cycle
- Cell Death
- Drug Resistance, Neoplasm
- Gene Expression Regulation, Neoplastic
- MAP Kinase Signaling System
- Molecular Chaperones
- Pancreatic Neoplasms
- Precision Medicine
- Thyroid Neoplasms
Oncogenic transformation requires reprogramming in signaling and metabolism, which inevitably causes cellular stress that places pressure on transforming cells to develop stress tolerance mechanisms. As such, malignant tumors might have successfully developed a protective mechanism and, if identified, this mechanism may be targeted for therapy. An important goal of Park lab research is to elucidate the molecular mechanisms underlying these events and to translate the knowledge into an advanced therapeutic strategy.
Dr. Park’s research projects include:
Studying the role of mortalin in MEK/ERK-activated tumor cells
The MEK/ERK pathway is a key effector of the oncogenic BRAF, KRAS, and receptor tyrosine kinases, and its deregulation is a central signature of many epithelial cancers. We recently demonstrated that MEK/ERK deregulation puts cells at risk of mitochondrial cell death, but that mortalin, a mitochondrial chaperone, can counteract this risk. Briefly, mortalin can determine the live/die decision in MEK/ERK-dependent tumor cells by regulating a mitochondrial death machinery that consists of ANT, a mitochondrial channel that controls bioenergetic homeostasis, and CypD, a chaperone that functions as the gatekeeper of the mitochondrial permeability transition pore (view article PMID: 32156782; view article PMID: 32291414). Current studies in Park lab focus on elucidating the nature of mitochondrial stress associated with overactive MEK/ERK signaling in tumor cells and on identifying the molecular mechanisms by which mortalin protects tumor cells from this stress.
Targeting mitochondrial metabolism in RET-mutant cancers
Somatic as well as inherited mutations in the RET receptor tyrosine kinase are a key etiological factor in cancers, including thyroid cancer. For example, inherited RET mutations are an important prognostic marker for the multiple endocrine neoplasia type 2 (MEN2) syndrome, in which medullary thyroid cancer is a key pathological presentation. As a member of the American Cancer Society MEN2 consortium, we recently demonstrated that mitochondrial bioenergetics is affected by RET inhibition in medullary thyroid tumor cells and that the mitochondrial activity altered upon RET inhibition can be exploited for the design of a combination therapy with mitochondria targeted agents (view article PMID: 28475408). Our current research focuses on further developing this concept in different tumors.
Participating 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 (view article PMID: 32758030). Find more information at the National Cancer Institute.
eIF5A-Independent Role of DHPS in p21CIP1 and Cell Fate Regulation.
(Becker AE, Wu PK, Park JI.) Int J Mol Sci. 2021 Dec 07;22(24) PMID: 34947982 PMCID: PMC8707118 SCOPUS ID: 2-s2.0-85120635476 12/25/2021
Mortalin depletion induces MEK/ERK-dependent and ANT/CypD-mediated death in vemurafenib-resistant B-RafV600E melanoma cells.
(Wu PK, Hong SK, Park JI.) Cancer Lett. 2021 Apr 01;502:25-33 PMID: 33440231 PMCID: PMC7897271 SCOPUS ID: 2-s2.0-85099283545 01/14/2021
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
(Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H, Abildgaard MH, Abudu YP, Acevedo-Arozena A, Adamopoulos IE, Adeli K, Adolph TE, Adornetto A, Aflaki E, Agam G, Agarwal A, Aggarwal BB, Agnello M, Agostinis P, Agrewala JN, Agrotis A, Aguilar PV, Ahmad ST, Ahmed ZM, Ahumada-Castro U, Aits S, Aizawa S, Akkoc Y, Akoumianaki T, Akpinar HA, Al-Abd AM, Al-Akra L, Al-Gharaibeh A, Alaoui-Jamali MA, Alberti S, Alcocer-Gómez E, Alessandri C, Ali M, Alim Al-Bari MA, Aliwaini S, Alizadeh J, Almacellas E, Almasan A, Alonso A, Alonso GD, Altan-Bonnet N, Altieri DC, Álvarez ÉMC, Alves S, Alves da Costa C, Alzaharna MM, Amadio M, Amantini C, Amaral C, Ambrosio S, Amer AO, Ammanathan V, An Z, Andersen SU, Andrabi SA, Andrade-Silva M, Andres AM, Angelini S, Ann D, Anozie UC, Ansari MY, Antas P, Antebi A, Antón Z, Anwar T, Apetoh L, Apostolova N, Araki T, Araki Y, Arasaki K, Araújo WL, Araya J, Arden C, Arévalo MA, Arguelles S, Arias E, Arikkath J, Arimoto H, Ariosa AR, Armstrong-James D, Arnauné-Pelloquin L, Aroca A, Arroyo DS, Arsov I, Artero R, Asaro DML, Aschner M, Ashrafizadeh M, Ashur-Fabian O, Atanasov AG, Au AK, Auberger P, Auner HW, Aurelian L, Autelli R, Avagliano L, Ávalos Y, Aveic S, Aveleira CA, Avin-Wittenberg T, Aydin Y, Ayton S, Ayyadevara S, Azzopardi M, Baba M, Backer JM, Backues SK, Bae DH, Bae ON, Bae SH, Baehrecke EH, Baek A, Baek SH, Baek SH, Bagetta G, Bagniewska-Zadworna A, Bai H, Bai J, Bai X, Bai Y, Bairagi N, Baksi S, Balbi T, Baldari CT, Balduini W, Ballabio A, Ballester M, Balazadeh S, Balzan R, Bandopadhyay R, Banerjee S, Banerjee S, Bánréti Á, Bao Y, Baptista MS, Baracca A, Barbati C, Bargiela A, Barilà D, Barlow PG, Barmada SJ, Barreiro E, Barreto GE, Bartek J, Bartel B, Bartolome A, Barve GR, Basagoudanavar SH, Bassham DC, Bast RC Jr, Basu A, Batoko H, Batten I, Baulieu EE, Baumgarner BL, Bayry J, Beale R, Beau I, Beaumatin F, Bechara LRG, Beck GR Jr, Beers MF, Begun J, Behrends C, Behrens GMN, Bei R, Bejarano E, Bel S, Behl C, Belaid A, Belgareh-Touzé N, Bellarosa C, Belleudi F, Belló Pérez M, Bello-Morales R, Beltran JSO, Beltran S, Benbrook DM, Bendorius M, Benitez BA, Benito-Cuesta I, Bensalem J, Berchtold MW, Berezowska S, Bergamaschi D, Bergami M, Bergmann A, Berliocchi L, Berlioz-Torrent C, Bernard A, Berthoux L, Besirli CG, Besteiro S, Betin VM, Beyaert R, Bezbradica JS, Bhaskar K, Bhatia-Kissova I, Bhattacharya R, Bhattacharya S, Bhattacharyya S, Bhuiyan MS, Bhutia SK, Bi L, Bi X, Biden TJ, Bijian K, Billes VA, Binart N, Bincoletto C, Birgisdottir AB, Bjorkoy G, Blanco G, Blas-Garcia A, Blasiak J, Blomgran R, Blomgren K, Blum JS, Boada-Romero E, Boban M, Boesze-Battaglia K, Boeuf P, Boland B, Bomont P, Bonaldo P, Bonam SR, Bonfili L, Bonifacino JS, Boone BA, Bootman MD, Bordi M, Borner C, Bornhauser BC, Borthakur G, Bosch J, Bose S, Botana LM, Botas J, Boulanger CM, Boulton ME, Bourdenx M, Bourgeois B, Bourke NM, Bousquet G, Boya P, Bozhkov PV, Bozi LHM, Bozkurt TO, Brackney DE, Brandts CH, Braun RJ, Braus GH, Bravo-Sagua R, Bravo-San Pedro JM, Brest P, Bringer MA, Briones-Herrera A, Broaddus VC, Brodersen P, Brodsky JL, Brody SL, Bronson PG, Bronstein JM, Brown CN, Brown RE, Brum PC, Brumell JH, Brunetti-Pierri N, Bruno D, Bryson-Richardson RJ, Bucci C, Buchrieser C, Bueno M, Buitrago-Molina LE, Buraschi S, Buch S, Buchan JR, Buckingham EM, Budak H, Budini M, Bultynck G, Burada F, Burgoyne JR, Burón MI, Bustos V, Büttner S, Butturini E, Byrd A, Cabas I, Cabrera-Benitez S, Cadwell K, Cai J, Cai L, Cai Q, Cairó M, Calbet JA, Caldwell GA, Caldwell KA, Call JA, Calvani R, Calvo AC, Calvo-Rubio Barrera M, Camara NO, Camonis JH, Camougrand N, Campanella M, Campbell EM, Campbell-Valois FX, Campello S, Campesi I, Campos JC, Camuzard O, Cancino J, Candido de Almeida D, Canesi L, Caniggia I, Canonico B, Cantí C, Cao B, Caraglia M, Caramés B, Carchman EH, Cardenal-Muñoz E, Cardenas C, Cardenas L, Cardoso SM, Carew JS, Carle GF, Carleton G, Carloni S, Carmo.) Autophagy. 2021 Jan;17(1):1-382 PMID: 33634751 PMCID: PMC7996087 SCOPUS ID: 2-s2.0-85102619204 02/27/2021
Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H.
(Salama AKS, Li S, Macrae ER, Park JI, Mitchell EP, Zwiebel JA, Chen HX, Gray RJ, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Armstrong DK, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT.) J Clin Oncol. 2020 Nov 20;38(33):3895-3904 PMID: 32758030 PMCID: PMC7676884 SCOPUS ID: 2-s2.0-85093919047 08/08/2020
Anticholestatic Effect of Bardoxolone Methyl on Hepatic Ischemia-reperfusion Injury in Rats.
(Kim J, Hagen CE, Kumar SN, Park JI, Zimmerman MA, Hong JC.) Transplant Direct. 2020 Aug;6(8):e584 PMID: 32766432 PMCID: PMC7371100 SCOPUS ID: 2-s2.0-85094858644 08/09/2020
Growth Inhibitory Signaling of the Raf/MEK/ERK Pathway.
(Wu PK, Becker A, Park JI.) Int J Mol Sci. 2020 Jul 30;21(15) PMID: 32751750 PMCID: PMC7432891 SCOPUS ID: 2-s2.0-85089131301 08/06/2020
Mortalin/HSPA9 targeting selectively induces KRAS tumor cell death by perturbing mitochondrial membrane permeability.
(Wu PK, Hong SK, Starenki D, Oshima K, Shao H, Gestwicki JE, Tsai S, Park JI.) Oncogene. 2020 May;39(21):4257-4270 PMID: 32291414 PMCID: PMC7244387 SCOPUS ID: 2-s2.0-85083767959 04/16/2020
Mortalin (HSPA9) facilitates BRAF-mutant tumor cell survival by suppressing ANT3-mediated mitochondrial membrane permeability.
(Wu PK, Hong SK, Chen W, Becker AE, Gundry RL, Lin CW, Shao H, Gestwicki JE, Park JI.) Sci Signal. 2020 Mar 10;13(622) PMID: 32156782 PMCID: PMC7099430 SCOPUS ID: 2-s2.0-85081677231 03/12/2020
Mortalin (GRP75/HSPA9) Promotes Survival and Proliferation of Thyroid Carcinoma Cells.
(Starenki D, Sosonkina N, Hong SK, Lloyd RV, Park JI.) Int J Mol Sci. 2019 Apr 26;20(9) PMID: 31027376 PMCID: PMC6540051 SCOPUS ID: 2-s2.0-85065295769 04/28/2019
Treatment of Cells and Tissues with Chromate Maximizes Mitochondrial 2Fe2S EPR Signals.
(Antholine WE, Vasquez-Vivar J, Quirk BJ, Whelan HT, Wu PK, Park JI, Myers CR.) Int J Mol Sci. 2019 Mar 06;20(5) PMID: 30845710 PMCID: PMC6429069 SCOPUS ID: 2-s2.0-85062628835 03/09/2019
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 PMID: 28986121 PMCID: PMC5732048 SCOPUS ID: 2-s2.0-85031106212 10/08/2017
Steady-State Levels of Phosphorylated Mitogen-Activated Protein Kinase Kinase 1/2 Determined by Mortalin/HSPA9 and Protein Phosphatase 1 Alpha in KRAS and BRAF Tumor Cells.
(Wu PK, Hong SK, Park JI.) Mol Cell Biol. 2017 Sep 15;37(18) PMID: 28674184 PMCID: PMC5574043 SCOPUS ID: 2-s2.0-85028363255 07/05/2017