Rosemary Akhurst, PhD

Professor In Residence
HDF Comprehensive Cancer Ctr
+1 415 514-0215

TGFβ signaling is important in cancer, vascular, and stem cell biology, as well as tumor drug-resistance and immunotherapy. We study how TGFβ regulates these processes in vivo, and how genetic variation affects TGFβ related diseases and drug outcomes.

Akhurst Lab

Publications: 

Stem-cell states converge in multistage cutaneous squamous cell carcinoma development.

Science (New York, N.Y.)

Taylor MA, Kandyba E, Halliwill K, Delrosario R, Khoroshkin M, Goodarzi H, Quigley D, Li YR, Wu D, Bollam SR, Mirzoeva OK, Akhurst RJ, Balmain A

Executive summary of the 14th HHT international scientific conference.

Angiogenesis

Ola R, Hessels J, Hammill A, Friday C, Clancy M, Al-Samkari H, Meadows S, Iyer V, Akhurst R

Gene networks reveal stem-cell state convergence during preneoplasia and progression to malignancy in multistage skin carcinogenesis.

bioRxiv : the preprint server for biology

Taylor MA, Kandyba E, Halliwill K, Delrosario R, Koroshkin M, Goodarzi H, Quigley D, Li YR, Wu D, Bollam S, Mirzoeva O, Akhurst RJ, Balmain A

Genetic polymorphism in Methylenetetrahydrofolate Reductase chloride transport protein 6 (MTHFR CLCN6) gene is associated with keratinocyte skin cancer in a cohort of renal transplant recipients.

Skin health and disease

Griffin L, Ho L, Akhurst RJ, Arron ST, Boggs JME, Conlon P, O'Kelly P, Toland AE, Epstein EH, Balmain A, Bastian BC, Moloney FJ, Murphy GM, Laing ME

TGF�: Signaling Blockade for Cancer Immunotherapy.

Annual review of cancer biology

Chen SY, Mamai O, Akhurst RJ

Integrin αvβ8 on T cells suppresses anti-tumor immunity in multiple models and is a promising target for tumor immunotherapy.

Cell reports

Dodagatta-Marri E, Ma HY, Liang B, Li J, Meyer DS, Chen SY, Sun KH, Ren X, Zivak B, Rosenblum MD, Headley MB, Pinzas L, Reed NI, Del Cid JS, Hann BC, Yang S, Giddabasappa A, Noorbehesht K, Yang B, Dal Porto J, Tsukui T, Niessen K, Atakilit A, Akhurst RJ, Sheppard D

TGFß biology in cancer progression and immunotherapy.

Nature reviews. Clinical oncology

Derynck R, Turley SJ, Akhurst RJ

a-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by a-TGFß antibody to promote durable rejection and immunity in squamous cell carcinomas.

Journal for immunotherapy of cancer

Dodagatta-Marri E, Meyer DS, Reeves MQ, Paniagua R, To MD, Binnewies M, Broz ML, Mori H, Wu D, Adoumie M, Del Rosario R, Li O, Buchmann T, Liang B, Malato J, Arce Vargus F, Sheppard D, Hann BC, Mirza A, Quezada SA, Rosenblum MD, Krummel MF, Balmain A, Akhurst RJ

Chronic TGF-ß exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition.

Science signaling

Katsuno Y, Meyer DS, Zhang Z, Shokat KM, Akhurst RJ, Miyazono K, Derynck R

Smad3-mediated recruitment of the methyltransferase SETDB1/ESET controls Snail1 expression and epithelial-mesenchymal transition.

EMBO reports

Du D, Katsuno Y, Meyer D, Budi EH, Chen SH, Koeppen H, Wang H, Akhurst RJ, Derynck R

Targeting TGF-ß Signaling for Therapeutic Gain.

Cold Spring Harbor perspectives in biology

Akhurst RJ

ShcA Protects against Epithelial-Mesenchymal Transition through Compartmentalized Inhibition of TGF-ß-Induced Smad Activation.

PLoS biology

Muthusamy BP, Budi EH, Katsuno Y, Lee MK, Smith SM, Mirza AM, Akhurst RJ, Derynck R

Defining Primary Marrow Microenvironment-Induced Synthetic Lethality and Resistance for 2,684 Approved Drugs Across Molecularly Distinct Forms of Multiple Myeloma.

Blood

Megan Murnane, Eugen Dhimolea, Ruojing Li, Megan A. Bariteau, Diamond D. Wheeler, Rosemary J. Akhurst, Aaron C. Logan, Pamela Munster, Arun Wiita, Thomas G. Martin, Jeffrey L. Wolf, Jun O. Liu, Constantine S. Mitsiades, Blake T. Aftab

Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14.

Frontiers in genetics

Letteboer TG, Benzinou M, Merrick CB, Quigley DA, Zhau K, Kim IJ, To MD, Jablons DM, van Amstel JK, Westermann CJ, Giraud S, Dupuis-Girod S, Lesca G, Berg JH, Balmain A, Akhurst RJ

Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking aVß8-TGFß signaling in the brain.

Development (Cambridge, England)

Arnold TD, Niaudet C, Pang MF, Siegenthaler J, Gaengel K, Jung B, Ferrero GM, Mukouyama YS, Fuxe J, Akhurst R, Betsholtz C, Sheppard D, Reichardt LF

Genetic variants of Adam17 differentially regulate TGFß signaling to modify vascular pathology in mice and humans.

Proceedings of the National Academy of Sciences of the United States of America

Kawasaki K, Freimuth J, Meyer DS, Lee MM, Tochimoto-Okamoto A, Benzinou M, Clermont FF, Wu G, Roy R, Letteboer TG, Ploos van Amstel JK, Giraud S, Dupuis-Girod S, Lesca G, Westermann CJ, Coffey RJ, Akhurst RJ

BMP-9 balances endothelial cell fate.

Proceedings of the National Academy of Sciences of the United States of America

Derynck R, Akhurst RJ

Multiple self-healing squamous epithelioma (MSSE): rare variants in an adjacent region of chromosome 9q22.3 to known TGFBR1 mutations suggest a digenic or multilocus etiology.

The Journal of investigative dermatology

Kang HC, Quigley DA, Kim IJ, Wakabayashi Y, Ferguson-Smith MA, D'Alessandro M, Birgitte Lane E, Akhurst RJ, Goudie DR, Balmain A

Erratum: Targeting the TGFß signalling pathway in disease.

Nature Reviews Drug Discovery

Rosemary J. Akhurst, Akiko Hata

Epistatic interactions between Tgfb1 and genetic loci, Tgfbm2 and Tgfbm3, determine susceptibility to an asthmatic stimulus.

Proceedings of the National Academy of Sciences of the United States of America

Freimuth J, Clermont FF, Huang X, DeSapio A, Tokuyasu TA, Sheppard D, Akhurst RJ

Targeting the TGFß signalling pathway in disease.

Nature reviews. Drug discovery

Akhurst RJ, Hata A

The paradoxical TGF-ß vasculopathies.

Nature genetics

Akhurst RJ

Complexities of TGF-ß targeted cancer therapy.

International journal of biological sciences

Connolly EC, Freimuth J, Akhurst RJ

TGF- -induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion.

Development

S. Lamouille, E. Connolly, J. W. Smyth, R. J. Akhurst, R. Derynck

TGF-ß-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion.

Journal of cell science

Lamouille S, Connolly E, Smyth JW, Akhurst RJ, Derynck R

Defective retinal vascular endothelial cell development as a consequence of impaired integrin aVß8-mediated activation of transforming growth factor-ß.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Arnold TD, Ferrero GM, Qiu H, Phan IT, Akhurst RJ, Huang EJ, Reichardt LF

Mouse and human strategies identify PTPN14 as a modifier of angiogenesis and hereditary haemorrhagic telangiectasia.

Nature communications

Benzinou M, Clermont FF, Letteboer TG, Kim JH, Espejel S, Harradine KA, Arbelaez J, Luu MT, Roy R, Quigley D, Higgins MN, Zaid M, Aouizerat BE, van Amstel JK, Giraud S, Dupuis-Girod S, Lesca G, Plauchu H, Hughes CC, Westermann CJ, Akhurst RJ

Erratum: Mouse and human strategies identify PTPN14 as a modifier of angiogenesis and hereditary haemorrhagic telangiectasia.

Nature communications

Michael Benzinou, Frederic F. Clermont, Tom G W. Letteboer, Jai-hyun Kim, Silvia Espejel, Kelly A. Harradine, Juan Arbelaez, Minh Thu Luu, Ritu Roy, David Quigley, Mamie Nakayama Higgins, Musa Zaid, Bradley E. Aouizerat, Johannes Kristian Ploos van Amstel, Sophie Giraud, Sophie Dupuis-Girod, Gaetan Lesca, Henri Plauchu, Christopher C W. Hughes, Cornelius J.J. Westermann, Rosemary J. Akhurst

The complexities of TGF-ß action during mammary and squamous cell carcinogenesis.

Current pharmaceutical biotechnology

Connolly EC, Akhurst RJ

TGFß1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo.

Clinical cancer research : an official journal of the American Association for Cancer Research

Bouquet F, Pal A, Pilones KA, Demaria S, Hann B, Akhurst RJ, Babb JS, Lonning SM, DeWyngaert JK, Formenti SC, Barcellos-Hoff MH

Outgrowth of drug-resistant carcinomas expressing markers of tumor aggression after long-term TßRI/II kinase inhibition with LY2109761.

Cancer research

Connolly EC, Saunier EF, Quigley D, Luu MT, De Sapio A, Hann B, Yingling JM, Akhurst RJ

Taking thalidomide out of rehab.

Nature medicine

Akhurst RJ

Elevated cutaneous Smad activation associates with enhanced skin tumor susceptibility in organ transplant recipients.

Clinical cancer research : an official journal of the American Association for Cancer Research

Harradine KA, Ridd K, Saunier EF, Clermont FF, Perez-Losada J, Moore DH, Epstein EH, Bastian BC, Akhurst RJ

Transforming growth factor-beta in breast cancer: too much, too late.

Breast cancer research : BCR

Barcellos-Hoff MH, Akhurst RJ

The type I TGF-beta receptor is covalently modified and regulated by sumoylation.

Nature cell biology

Kang JS, Saunier EF, Akhurst RJ, Derynck R

Reversal of EMT by Small-Molecule Inhibitors of TGF-ß Type I and II Receptors: Implications for Carcinoma Treatment.

Transforming Growth Factor-ß in Cancer Therapy, Volume II

Markus D. Lacher, W. Michael Korn, Rosemary J. Akhurst

Characterization of Tgfbm2, a genetic modifier of Tgfb1-/- embryonic lethality.

The FASEB Journal

Frederic Clermont, Minh Thu Luu, Mamie Higgins, Rosemary J Akhurst

TGF beta inhibition for cancer therapy.

Current cancer drug targets

Saunier EF, Akhurst RJ

Large- and small-molecule inhibitors of transforming growth factor-beta signaling.

Current opinion in investigational drugs (London, England : 2000)

Akhurst RJ

Genetic variants of Tgfb1 act as context-dependent modifiers of mouse skin tumor susceptibility.

Proceedings of the National Academy of Sciences of the United States of America

Mao JH, Saunier EF, de Koning JP, McKinnon MM, Higgins MN, Nicklas K, Yang HT, Balmain A, Akhurst RJ

Mutations of TGFbeta signaling molecules in human disease.

Annals of medicine

Harradine KA, Akhurst RJ

Epistatic interactions between modifier genes confer strain-specific redundancy for Tgfb1 in developmental angiogenesis.

Genomics

Tang Y, Lee KS, Yang H, Logan DW, Wang S, McKinnon ML, Holt LJ, Condie A, Luu MT, Akhurst RJ

TGF beta signaling in health and disease.

Nature genetics

Akhurst RJ

Cancer: dangerous liaisons.

Nature

Balmain A, Akhurst RJ

Mouse strain-dependent heterogeneity of resting limbal vasculature.

Investigative ophthalmology & visual science

Chan CK, Pham LN, Chinn C, Spee C, Ryan SJ, Akhurst RJ, Hinton DR

Genetic modifiers interact with maternal determinants in vascular development of Tgfb1(-/-) mice.

Human molecular genetics

Tang Y, McKinnon ML, Leong LM, Rusholme SA, Wang S, Akhurst RJ

Transforming growth factor-beta1 mediates cellular response to DNA damage in situ.

Cancer research

Ewan KB, Henshall-Powell RL, Ravani SA, Pajares MJ, Arteaga C, Warters R, Akhurst RJ, Barcellos-Hoff MH

Metastasis is driven by sequential elevation of H-ras and Smad2 levels.

Nature cell biology

Oft M, Akhurst RJ, Balmain A

Latent transforming growth factor-beta activation in mammary gland: regulation by ovarian hormones affects ductal and alveolar proliferation.

The American journal of pathology

Ewan KB, Shyamala G, Ravani SA, Tang Y, Akhurst R, Wakefield L, Barcellos-Hoff MH

TGF-beta antagonists: why suppress a tumor suppressor?

The Journal of clinical investigation

Akhurst RJ

TGF-beta signaling in cancer--a double-edged sword.

Trends in cell biology

Akhurst RJ, Derynck R

TGF-ß signaling in cancer — a double-edged sword.

Trends in cell biology

Rosemary J. Akhurst, Rik Derynck

TGF-beta signaling in tumor suppression and cancer progression.

Nature genetics

Derynck R, Akhurst RJ, Balmain A

Isolation, identification, and molecular characterization of strains of Photorhabdus luminescens from infected humans in Australia.

Journal of clinical microbiology

Peel MM, Alfredson DA, Gerrard JG, Davis JM, Robson JM, McDougall RJ, Scullie BL, Akhurst RJ

Epithelial carcinogenesis in the mouse: correlating the genetics and the biology.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

Frame S, Crombie R, Liddell J, Stuart D, Linardopoulos S, Nagase H, Portella G, Brown K, Street A, Akhurst R, Balmain A

Transforming growth factor beta is essential for spindle cell conversion of mouse skin carcinoma in vivo: implications for tumor invasion.

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research

Portella G, Cumming SA, Liddell J, Cui W, Ireland H, Akhurst RJ, Balmain A

Mapping of a major genetic modifier of embryonic lethality in TGF beta 1 knockout mice.

Nature genetics

Bonyadi M, Rusholme SA, Cousins FM, Su HC, Biron CA, Farrall M, Akhurst RJ

Altered epidermal cell growth control in vivo by inducible expression of transforming growth factor beta 1 in the skin of transgenic mice.

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research

Fowlis DJ, Cui W, Johnson SA, Balmain A, Akhurst RJ

The TGF beta type II receptor, Tgfbr2, maps to distal mouse chromosome 9.

Genomics

Bonyadi M, Cui W, Nagase H, Akhurst RJ

The role of transforming growth factor ß during cardiovascular development.

Molecular Physiology of Growth

Marion C. Dickson, Julie S. Martin, Rosemary J. Akhurst

Liposome-medicated gene transfer and expression via the skin.

Human molecular genetics

Alexander MY, Akhurst RJ

Circulating human factor IX produced in keratin-promoter transgenic mice: a feasibility study for gene therapy of haemophilia B.

Human molecular genetics

Alexander MY, Bidichandani SI, Cousins FM, Robinson CJ, Duffie E, Akhurst RJ

Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice.

Development (Cambridge, England)

Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ

Concerted action of TGF-beta 1 and its type II receptor in control of epidermal homeostasis in transgenic mice.

Genes & development

Cui W, Fowlis DJ, Cousins FM, Duffie E, Bryson S, Balmain A, Akhurst RJ

Analysis of homozygous TGF beta 1 null mouse embryos demonstrates defects in yolk sac vasculogenesis and hematopoiesis.

Annals of the New York Academy of Sciences

Martin JS, Dickson MC, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ

Localization of transforming growth factor-alpha RNA and protein in the skin of psoriatic patients receiving therapy.

The British journal of dermatology

Watts P, Stables GS, Akhurst RJ, Mackie RM

Physical methods of gene delivery using keratinocytes as a target for somatic cell gene therapy.

Gene therapy

Alexander MY, Bidichandani S, Robinson C, Trainer AH, Akhurst RJ

RNA and protein localisations of TGF beta 2 in the early mouse embryo suggest an involvement in cardiac development.

Development (Cambridge, England)

Dickson MC, Slager HG, Duffie E, Mummery CL, Akhurst RJ

Positive and negative growth control in multistage skin carcinogenesis.

Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer

Brown K, Kemp CJ, Burns PA, Stoler AB, Fowlis DJ, Akhurst RJ, Balmain A

Rapid induction and clearance of TGF beta 1 is an early response to wounding in the mouse embryo.

Developmental genetics

Martin P, Dickson MC, Millan FA, Akhurst RJ

Transforming growth factor ßs and cardiac development.

Growth Factors and the Cardiovascular System

Rosemary J. Akhurst, Marion Dickson, Fergus A. Millan

The role of TGF-beta s in mammalian development and neoplasia.

Molecular reproduction and development

Akhurst RJ, Fitzpatrick DR, Fowlis DJ, Gatherer D, Millan FA, Slager H

Palatal expression of TGF-ß isoforms in normal and retinoic acid-treated mouse embryos.

Retinoids in Normal Development and Teratogenesis

David R FitzPatrick, Barbara D Abbott, Rosemary J Akhurst

Discordant transforming growth factor beta 1 RNA and protein localization during chemical carcinogenesis of the skin.

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research

Fowlis DJ, Flanders KC, Duffie E, Balmain A, Akhurst RJ

Functional loss of tumour suppressor genes in multistage chemical carcinogenesis.

Princess Takamatsu symposia

Balmain A, Kemp CJ, Burns PA, Stoler AB, Fowlis DJ, Akhurst RJ

Expression of TGF-beta isoforms during first trimester human embryogenesis.

Development (Cambridge, England)

Gatherer D, Ten Dijke P, Baird DT, Akhurst RJ

Localization of elevated transforming growth factor-alpha in psoriatic epidermis.

The Journal of investigative dermatology

Turbitt ML, Akhurst RJ, White SI, MacKie RM

Differential expression of TGF beta isoforms in murine palatogenesis.

Development (Cambridge, England)

Fitzpatrick DR, Denhez F, Kondaiah P, Akhurst RJ

TGF beta in murine morphogenetic processes: the early embryo and cardiogenesis.

Development (Cambridge, England)

Akhurst RJ, Lehnert SA, Faissner A, Duffie E

The role of TGF beta in mouse development.

Annals of the New York Academy of Sciences

Akhurst RJ, Lehnert SA, Gatherer D, Duffie E

Transforming growth factor betas in mammalian embryogenesis.

Progress in growth factor research

Akhurst RJ, FitzPatrick DR, Gatherer D, Lehnert SA, Millan FA

The role of transforming growth factor-ß in mouse development and carcinogenesis.

Biochemical Society transactions

ROSEMARY J. AKHURST, SIGRID A. LEHNERT, FRANCES FEE, ALLAN BALMAIN

Chemical induction of oncogene mutations and growth factor activity in mouse skin carcinogenesis.

Environmental health perspectives

Bailleul B, Brown K, Ramsden M, Akhurst RJ, Fee F, Balmain A

Intracellular localisation and expression of mammalian CDC2 protein during myogenic differentiation.

Differentiation; research in biological diversity

Akhurst RJ, Flavin NB, Worden J, Lee MG

Prospects for Gene Therapy Now and in the Future.

Studies in Inherited Metabolic Disease

R. J. Akhurst

Prospects for gene therapy now and in the future.

Journal of inherited metabolic disease

Akhurst RJ

The action of oncogenes and growth factors in tumour initiation and promotion.

Carcinogenesis; a comprehensive survey

Akhurst R, Bailleul B, Brown K, Ramsden M, Fee F, Balmain A

Molecular analysis of chemical carcinogenesis in the skin.

The British journal of cancer. Supplement

Balmain A, Brown K, Akhurst RJ, Fee FM

Chorionic gonadotrophin-beta mRNA, a trophoblast marker, is expressed in human 8-cell embryos derived from tripronucleate zygotes.

Human reproduction (Oxford, England)

Bonduelle ML, Dodd R, Liebaers I, Van Steirteghem A, Williamson R, Akhurst R

Isolation and Characterization of a Variant Myoblast Cell Line That is Temperature Sensitive for Differentiation.

Molecular and cellular biology

Rosemary J. Akhurst, Nora B. Flavin, Jenny Worden

Sea urchin actin gene linkages determined by genetic segregation.

Developmental biology

Minor JE, Lee JJ, Akhurst RJ, Leahy PS, Britten RJ, Davidson EH

Structure and organization of the CyIII actin gene subfamily of the sea urchin, Strongylocentrotus purpuratus.

Journal of molecular biology

Akhurst RJ, Calzone FJ, Lee JJ, Britten RJ, Davidson EH

The use of gene probes in studying human reproduction and embryology.

Human reproduction (Oxford, England)

Akhurst RJ

Sea urchin actin gene subtypes. Gene number, linkage and evolution.

Journal of molecular biology

Lee JJ, Shott RJ, Rose SJ, Thomas TL, Britten RJ, Davidson EH

Dev. Biol

Differential expression of the actin gene family of Strongylocentrotus purpuratus

Akhurst RJ (Shott RJ) Lee JJ, Britten RJ, Davidson EH

Regulation of the relative abundances of mRNAs in hepatoma and liver.

Advances in experimental medicine and biology

Birnie GD, Jacobs H, Shott R, Wilkes PR

Post-transcriptional control of messenger abundance.

Molecular biology reports

Birnie GD, Balmain A, Jacobs H, Shott R, Wilkes PR, Paul J