Kay Macleod, PhD

The deadliest aspect of the majority of human cancers is metastasis, the multi-step process by which cancer cells escape the confines of the primary site (such as breast, pancreas or other organs) and travel in the circulation to distant sites (such as brain, liver or lungs) where they can lodge, invade and grow out as secondary tumors or metastases.

Many factors play into cancer metastasis including how disseminating tumor cells respond to stresses such as nutrient deprivation and altered cellular attachments. These stresses are known to activate a process known as autophagy and research in the Macleod Lab seeks to understand and clarify the role of autophagy in tumor growth and progression to metastasis. In particular, we are interested in understanding how defects in the turnover of mitochondria (the energy factory of the cell) by autophagy, leads to tumor invasion and metastasis.

Using a variety of approaches from biochemical, molecular, cellular as well as genetic models to in vivo imaging and primary human patient sample analysis, research on the role of autophagy in cancer metastasis in the Macleod Lab is focused on breast cancer, pancreatic cancer and liver cancer. By examining and comparing similarities and differences between how metastasis develops from each of these organ sites, we can appreciate what new molecular targets may be most relevant to understanding and ultimately treating these deadly diseases.

University of Edinburgh
Scotland
B.Sc. (Hons) - Molecular Biology
07/1986

The Beatson Institute for Cancer Research, University of Glasgow
Scotland
Ph.D. - Cancer Biology
07/1990

Institut Pasteur
France
Post-doctoral fellow - Ets Transcription Factors
03/1993

The Massachusetts Institute of Technology
Cambridge, MA
Post-doctoral fellow - The RB tumor suppressor
09/1996

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, Basu A, Batista MT, Batoko H, Battino M, Bauckman K, Baumgarner BL, Bayer KU, Beale R, Beaulieu JF, Beck GR, 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, Cianfanelli V, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016; 12(1):1-222.
PMID: 26799652

Autophagy, cancer stem cells and drug resistance.
Smith AG, Macleod KF. Autophagy, cancer stem cells and drug resistance. J Pathol. 2019 Apr; 247(5):708-718.
PMID: 30570140

Dia1-dependent adhesions are required by epithelial tissues to initiate invasion.
Fessenden TB, Beckham Y, Perez-Neut M, Ramirez-San Juan G, Chourasia AH, Macleod KF, Oakes PW, Gardel ML. Dia1-dependent adhesions are required by epithelial tissues to initiate invasion. J Cell Biol. 2018 04 02; 217(4):1485-1502.
PMID: 29437785

Functions of autophagy in the tumor microenvironment and cancer metastasis.
Mowers EE, Sharifi MN, Macleod KF. Functions of autophagy in the tumor microenvironment and cancer metastasis. FEBS J. 2018 05; 285(10):1751-1766.
PMID: 29356327

Active and dynamic mitochondrial S-depalmitoylation revealed by targeted fluorescent probes.
Kathayat RS, Cao Y, Elvira PD, Sandoz PA, Zaballa ME, Springer MZ, Drake LE, Macleod KF, van der Goot FG, Dickinson BC. Active and dynamic mitochondrial S-depalmitoylation revealed by targeted fluorescent probes. Nat Commun. 2018 01 23; 9(1):334.
PMID: 29362370

mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors.
Malone CF, Emerson C, Ingraham R, Barbosa W, Guerra S, Yoon H, Liu LL, Michor F, Haigis M, Macleod KF, Maertens O, Cichowski K. mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors. Cancer Discov. 2017 12; 7(12):1450-1463.
PMID: 28963352

Expanding perspectives on the significance of mitophagy in cancer.
Drake LE, Springer MZ, Poole LP, Kim CJ, Macleod KF. Expanding perspectives on the significance of mitophagy in cancer. Semin Cancer Biol. 2017 12; 47:110-124.
PMID: 28450176

Small molecules inhibit STAT3 activation, autophagy, and cancer cell anchorage-independent growth.
Zhou D, Springer MZ, Xu D, Liu D, Hudmon A, Macleod KF, Meroueh SO. Small molecules inhibit STAT3 activation, autophagy, and cancer cell anchorage-independent growth. Bioorg Med Chem. 2017 06 15; 25(12):2995-3005.
PMID: 28438385

Autophagy gene ATG7 regulates ultraviolet radiation-induced inflammation and skin tumorigenesis.
Qiang L, Sample A, Shea CR, Soltani K, Macleod KF, He YY. Autophagy gene ATG7 regulates ultraviolet radiation-induced inflammation and skin tumorigenesis. Autophagy. 2017; 13(12):2086-2103.
PMID: 28933598

In Brief: Mitophagy: mechanisms and role in human disease.
Springer MZ, Macleod KF. In Brief: Mitophagy: mechanisms and role in human disease. J Pathol. 2016 11; 240(3):253-255.
PMID: 27453450

View All Publications