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.

We are particularly interested in understanding how defects in the turnover of mitochondria (the energy factory of the cell) by mitophagy, leads to tumor invasion and metastasis. Our research addresses how mitophagy is induced and how mitophagy contributes to cellular homeostasis. This includes examining how physiological stresses, such as hypoxia and nutrient deprivation remodel the mitochondrial reticulum, how mitochondrial stress is sensed in the cell and how mitophagy is coordinated with other mitochondrial quality control pathways to promote cellular function. These mechanisms are frequently deregulated in cancers and research in the Macleod Lab also examines how defective mitophagy and mitochondrial dysfunction contributes to tumor progression and metastasis. Mitochondria are highly dynamic organelles and while their function in metabolism and control of apoptosis is well known, work in the Macleod Lab also examines how mitochondria modulate cell fate more broadly, including stemness and in metaplasia, and how they modulate cell motility and invasiveness. This is performed using novel mouse models, engineered cell lines and primary human tumor samples with a focus on breast, pancreas and liver cancers.

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

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

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

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

ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3.
Poole LP, Bock-Hughes A, Berardi DE, Macleod KF. ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3. Sci Rep. 2021 10 15; 11(1):20526.
PMID: 34654847

Autophagy in major human diseases.
Klionsky DJ, Petroni G, Amaravadi RK, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cadwell K, Cecconi F, Choi AMK, Choi ME, Chu CT, Codogno P, Colombo MI, Cuervo AM, Deretic V, Dikic I, Elazar Z, Eskelinen EL, Fimia GM, Gewirtz DA, Green DR, Hansen M, Jäättelä M, Johansen T, Juhász G, Karantza V, Kraft C, Kroemer G, Ktistakis NT, Kumar S, Lopez-Otin C, Macleod KF, Madeo F, Martinez J, Meléndez A, Mizushima N, Münz C, Penninger JM, Perera RM, Piacentini M, Reggiori F, Rubinsztein DC, Ryan KM, Sadoshima J, Santambrogio L, Scorrano L, Simon HU, Simon AK, Simonsen A, Stolz A, Tavernarakis N, Tooze SA, Yoshimori T, Yuan J, Yue Z, Zhong Q, Galluzzi L, Pietrocola F. Autophagy in major human diseases. EMBO J. 2021 10 01; 40(19):e108863.
PMID: 34459017

Mitophagy in tumorigenesis and metastasis.
Poole LP, Macleod KF. Mitophagy in tumorigenesis and metastasis. Cell Mol Life Sci. 2021 Apr; 78(8):3817-3851.
PMID: 33580835

BNIP3-dependent mitophagy promotes cytosolic localization of LC3B and metabolic homeostasis in the liver.
Springer MZ, Poole LP, Drake LE, Bock-Hughes A, Boland ML, Smith AG, Hart J, Chourasia AH, Liu I, Bozek G, Macleod KF. BNIP3-dependent mitophagy promotes cytosolic localization of LC3B and metabolic homeostasis in the liver. Autophagy. 2021 11; 17(11):3530-3546.
PMID: 33459136

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, Basu A, Batoko H, Batten I, Baulieu EE, Baumgarner BL, Bayry J, Beale R, Beau I, Beaumatin F, Bechara LRG, Beck GR, 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, Carmona-Gutierrez D, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021 Feb 08; 1-382.
PMID: 33634751

Somatic mitochondrial mutation discovery using ultra-deep sequencing of the mitochondrial genome reveals spatial tumor heterogeneity in head and neck squamous cell carcinoma.
Schubert AD, Channah Broner E, Agrawal N, London N, Pearson A, Gupta A, Wali N, Seiwert TY, Wheelan S, Lingen M, Macleod K, Allen H, Chatterjee A, Vassiliki S, Gaykalova D, Hoque MO, Sidransky D, Suresh K, Izumchenko E. Somatic mitochondrial mutation discovery using ultra-deep sequencing of the mitochondrial genome reveals spatial tumor heterogeneity in head and neck squamous cell carcinoma. Cancer Lett. 2020 02 28; 471:49-60.
PMID: 31830557

Autophagy and cancer cell metabolism.
Anderson CM, Macleod KF. Autophagy and cancer cell metabolism. Int Rev Cell Mol Biol. 2019; 347:145-190.
PMID: 31451213

Oncogenic KRAS Induces NIX-Mediated Mitophagy to Promote Pancreatic Cancer.
Humpton TJ, Alagesan B, DeNicola GM, Lu D, Yordanov GN, Leonhardt CS, Yao MA, Alagesan P, Zaatari MN, Park Y, Skepper JN, Macleod KF, Perez-Mancera PA, Murphy MP, Evan GI, Vousden KH, Tuveson DA. Oncogenic KRAS Induces NIX-Mediated Mitophagy to Promote Pancreatic Cancer. Cancer Discov. 2019 09; 9(9):1268-1287.
PMID: 31263025

Autophagy, cancer stem cells and drug resistance.
Smith AG, Macleod KF. Autophagy, cancer stem cells and drug resistance. J Pathol. 2019 04; 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

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