Biography Currently, I hold the position of Professor of Anatomy within the HDF Comprehensive Cancer Center at UCSF. My research work delves into the involvement of TGFbeta signaling pathway components in vascular biology and cancer. I have also taken on the role of Principal Investigator in numerous research projects funded by the NIH, focusing on areas like vascular stability, cancer immunotherapy, and vascular pathobiology. As part of my ongoing work, I am an active participant in projects aimed at reducing cancer health disparities and furthering our understanding of cancer progression. This journey into discovery and understanding is ongoing and I am continually learning and expanding upon my research. Publications Diverse Biological Processes Contribute to Transforming Growth Factor ß-Mediated Cancer Drug Resistance. James P. Heiserman, Rosemary J. Akhurst Abstract A055: Dissecting mechanisms of tumor anti-PD1 resistance due to host genetic variation within ADAM17. James P Heiserman, Rosemary Akhurst, Tanuja Desai, Sharon Chen Stem-cell states converge in multistage cutaneous squamous cell carcinoma development. 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 From shape-shifting embryonic cells to oncology: The fascinating history of epithelial mesenchymal transition. Akhurst RJ Executive summary of the 14th HHT international scientific conference. 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. 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 Abstract 3420: Tgfbm3b is a natural germline genetic variant that modifies anti-tumor responses to anti-PD-1 immunotherapy through its action on the tumor microenvironment. Szu-Ying Chen, Ons Mamai, Rosemary Akhurst 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. 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 TGFβ: Signaling Blockade for Cancer Immunotherapy. 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. 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 TGFβ biology in cancer progression and immunotherapy. Derynck R, Turley SJ, Akhurst RJ α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas. 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-β exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition. Katsuno Y, Meyer DS, Zhang Z, Shokat KM, Akhurst RJ, Miyazono K, Derynck R Enhanced TGF-β Signaling Contributes to the Insulin-Induced Angiogenic Responses of Endothelial Cells. Budi EH, Mamai O, Hoffman S, Akhurst RJ, Derynck R From prevention to cure, repurposing anti-viral vaccines for cancer immunotherapy. Mamai O, Dodagatta-Marri E, Akhurst RJ Smad3-mediated recruitment of the methyltransferase SETDB1/ESET controls Snail1 expression and epithelial-mesenchymal transition. Du D, Katsuno Y, Meyer D, Budi EH, Chen SH, Koeppen H, Wang H, Akhurst RJ, Derynck R Targeting TGF-β Signaling for Therapeutic Gain. Akhurst RJ ShcA Protects against Epithelial-Mesenchymal Transition through Compartmentalized Inhibition of TGF-β-Induced Smad Activation. 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. 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 Matters of context guide future research in TGFβ superfamily signaling. Akhurst RJ, Padgett RW 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. 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 αVβ8-TGFβ signaling in the brain. 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 TGFβ signaling to modify vascular pathology in mice and humans. 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. 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. 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. Rosemary J. Akhurst, Akiko Hata Epistatic interactions between Tgfb1 and genetic loci, Tgfbm2 and Tgfbm3, determine susceptibility to an asthmatic stimulus. Freimuth J, Clermont FF, Huang X, DeSapio A, Tokuyasu TA, Sheppard D, Akhurst RJ Targeting the TGFβ signalling pathway in disease. Akhurst RJ, Hata A The paradoxical TGF-β vasculopathies. Akhurst RJ Complexities of TGF-β targeted cancer therapy. Connolly EC, Freimuth J, Akhurst RJ TGF- -induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion. S. Lamouille, E. Connolly, J. W. Smyth, R. J. Akhurst, R. Derynck TGF-β-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion. Lamouille S, Connolly E, Smyth JW, Akhurst RJ, Derynck R Defective retinal vascular endothelial cell development as a consequence of impaired integrin αVβ8-mediated activation of transforming growth factor-β. 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. 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. 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-β action during mammary and squamous cell carcinogenesis. Connolly EC, Akhurst RJ TGFβ1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo. 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 TβRI/II kinase inhibition with LY2109761. Connolly EC, Saunier EF, Quigley D, Luu MT, De Sapio A, Hann B, Yingling JM, Akhurst RJ Taking thalidomide out of rehab. Akhurst RJ Elevated cutaneous Smad activation associates with enhanced skin tumor susceptibility in organ transplant recipients. 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. Barcellos-Hoff MH, Akhurst RJ The type I TGF-beta receptor is covalently modified and regulated by sumoylation. 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. Markus D. Lacher, W. Michael Korn, Rosemary J. Akhurst Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Derynck R, Akhurst RJ Characterization of Tgfbm2, a genetic modifier of Tgfb1-/- embryonic lethality. Frederic Clermont, Minh Thu Luu, Mamie Higgins, Rosemary J Akhurst TGF beta inhibition for cancer therapy. Saunier EF, Akhurst RJ Large- and small-molecule inhibitors of transforming growth factor-beta signaling. Akhurst RJ Genetic variants of Tgfb1 act as context-dependent modifiers of mouse skin tumor susceptibility. Mao JH, Saunier EF, de Koning JP, McKinnon MM, Higgins MN, Nicklas K, Yang HT, Balmain A, Akhurst RJ A sweet link between TGFbeta and vascular disease? Akhurst RJ Transforming growth factor-beta receptor inhibition enhances adenoviral infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus Receptor in conjunction with reversal of epithelial-mesenchymal transition. Lacher MD, Tiirikainen MI, Saunier EF, Christian C, Anders M, Oft M, Balmain A, Akhurst RJ, Korn WM TGFbeta inhibition of yolk-sac-like differentiation of human embryonic stem-cell-derived embryoid bodies illustrates differences between early mouse and human development. Poon E, Clermont F, Firpo MT, Akhurst RJ Mutations of TGFbeta signaling molecules in human disease. Harradine KA, Akhurst RJ Epistatic interactions between modifier genes confer strain-specific redundancy for Tgfb1 in developmental angiogenesis. 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. Akhurst RJ Cancer: dangerous liaisons. Balmain A, Akhurst RJ Mouse strain-dependent heterogeneity of resting limbal vasculature. 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. Tang Y, McKinnon ML, Leong LM, Rusholme SA, Wang S, Akhurst RJ Transforming growth factor-beta1 mediates cellular response to DNA damage in situ. 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. Oft M, Akhurst RJ, Balmain A Latent transforming growth factor-beta activation in mammary gland: regulation by ovarian hormones affects ductal and alveolar proliferation. Ewan KB, Shyamala G, Ravani SA, Tang Y, Akhurst R, Wakefield L, Barcellos-Hoff MH TGF-beta antagonists: why suppress a tumor suppressor? Akhurst RJ TGF-beta signaling in cancer--a double-edged sword. Akhurst RJ, Derynck R TGF-ß signaling in cancer — a double-edged sword. Rosemary J. Akhurst, Rik Derynck TGF-beta signaling in tumor suppression and cancer progression. Derynck R, Akhurst RJ, Balmain A Isolation, identification, and molecular characterization of strains of Photorhabdus luminescens from infected humans in Australia. Peel MM, Alfredson DA, Gerrard JG, Davis JM, Robson JM, McDougall RJ, Scullie BL, Akhurst RJ Genetic events and the role of TGF beta in epithelial tumour progression. Akhurst RJ, Balmain A Epithelial carcinogenesis in the mouse: correlating the genetics and the biology. 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. 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. Bonyadi M, Rusholme SA, Cousins FM, Su HC, Biron CA, Farrall M, Akhurst RJ TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cui W, Fowlis DJ, Bryson S, Duffie E, Ireland H, Balmain A, Akhurst RJ Altered epidermal cell growth control in vivo by inducible expression of transforming growth factor beta 1 in the skin of transgenic mice. Fowlis DJ, Cui W, Johnson SA, Balmain A, Akhurst RJ The TGF beta type II receptor, Tgfbr2, maps to distal mouse chromosome 9. Bonyadi M, Cui W, Nagase H, Akhurst RJ The role of transforming growth factor ß during cardiovascular development. Marion C. Dickson, Julie S. Martin, Rosemary J. Akhurst Transforming growth factor ßS: Biochemistry and biological activities in vitro and in vivo. Wei Cui, Rosemary J. Akhurst Liposome-medicated gene transfer and expression via the skin. Alexander MY, Akhurst RJ Circulating human factor IX produced in keratin-promoter transgenic mice: a feasibility study for gene therapy of haemophilia B. 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. 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. 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. Martin JS, Dickson MC, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ Lack of transforming growth factor-beta 1 expression in benign skin tumors of p53null mice is prognostic for a high risk of malignant conversion. Cui W, Kemp CJ, Duffie E, Balmain A, Akhurst RJ Localization of transforming growth factor-alpha RNA and protein in the skin of psoriatic patients receiving therapy. Watts P, Stables GS, Akhurst RJ, Mackie RM Physical methods of gene delivery using keratinocytes as a target for somatic cell gene therapy. Alexander MY, Bidichandani S, Robinson C, Trainer AH, Akhurst RJ Localization of growth factor mRNA in tissue sections by in situ hybridization. Rosemary J Akhurst RNA and protein localisations of TGF beta 2 in the early mouse embryo suggest an involvement in cardiac development. Dickson MC, Slager HG, Duffie E, Mummery CL, Akhurst RJ Positive and negative growth control in multistage skin carcinogenesis. 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. Martin P, Dickson MC, Millan FA, Akhurst RJ Transforming growth factor ßs and cardiac development. Rosemary J. Akhurst, Marion Dickson, Fergus A. Millan The role of TGF-beta s in mammalian development and neoplasia. 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. 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. Fowlis DJ, Flanders KC, Duffie E, Balmain A, Akhurst RJ Enormous scope for further research peptide growth factors and their receptors vol. I (1990). Edited by M. B. Sporn and A. B. Roberts. Springer-Verlag: Berlin. 785pp. DM 398. ISBN 3 540 51184 9. Rosemary Akhurst Loss of growth control by TGF-beta occurs at a late stage of mouse skin carcinogenesis and is independent of ras gene activation. Haddow S, Fowlis DJ, Parkinson K, Akhurst RJ, Balmain A Embryonic gene expression patterns of TGF beta 1, beta 2 and beta 3 suggest different developmental functions in vivo. Millan FA, Denhez F, Kondaiah P, Akhurst RJ Functional loss of tumour suppressor genes in multistage chemical carcinogenesis. Balmain A, Kemp CJ, Burns PA, Stoler AB, Fowlis DJ, Akhurst RJ Expression of TGF-beta isoforms during first trimester human embryogenesis. Gatherer D, Ten Dijke P, Baird DT, Akhurst RJ Localization of elevated transforming growth factor-alpha in psoriatic epidermis. Turbitt ML, Akhurst RJ, White SI, MacKie RM Differential expression of TGF beta isoforms in murine palatogenesis. Fitzpatrick DR, Denhez F, Kondaiah P, Akhurst RJ TGF beta in murine morphogenetic processes: the early embryo and cardiogenesis. Akhurst RJ, Lehnert SA, Faissner A, Duffie E The role of TGF beta in mouse development. Akhurst RJ, Lehnert SA, Gatherer D, Duffie E Transforming growth factor betas in mammalian embryogenesis. Akhurst RJ, FitzPatrick DR, Gatherer D, Lehnert SA, Millan FA The role of transforming growth factor-ß in mouse development and carcinogenesis. ROSEMARY J. AKHURST, SIGRID A. LEHNERT, FRANCES FEE, ALLAN BALMAIN Chemical induction of oncogene mutations and growth factor activity in mouse skin carcinogenesis. Bailleul B, Brown K, Ramsden M, Akhurst RJ, Fee F, Balmain A Intracellular localisation and expression of mammalian CDC2 protein during myogenic differentiation. Akhurst RJ, Flavin NB, Worden J, Lee MG Prospects for Gene Therapy Now and in the Future. R. J. Akhurst Prospects for gene therapy now and in the future. Akhurst RJ The action of oncogenes and growth factors in tumour initiation and promotion. Akhurst R, Bailleul B, Brown K, Ramsden M, Fee F, Balmain A Molecular analysis of chemical carcinogenesis in the skin. 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. Bonduelle ML, Dodd R, Liebaers I, Van Steirteghem A, Williamson R, Akhurst R Embryonic expression pattern of TGF beta type-1 RNA suggests both paracrine and autocrine mechanisms of action. Lehnert SA, Akhurst RJ Isolation and Characterization of a Variant Myoblast Cell Line That is Temperature Sensitive for Differentiation. Rosemary J. Akhurst, Nora B. Flavin, Jenny Worden Isolation and characterization of a variant myoblast cell line that is temperature sensitive for differentiation. Akhurst RJ, Flavin NB, Worden J Isolation and characterization of a variant myoblast cell line that is temperature sensitive for differentiation. R J Akhurst, N B Flavin, J Worden Localized production of TGF-beta mRNA in tumour promoter-stimulated mouse epidermis. Akhurst RJ, Fee F, Balmain A Sea urchin actin gene linkages determined by genetic segregation. 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. Akhurst RJ, Calzone FJ, Lee JJ, Britten RJ, Davidson EH The use of gene probes in studying human reproduction and embryology. Akhurst RJ Sea urchin actin gene subtypes. Gene number, linkage and evolution. Lee JJ, Shott RJ, Rose SJ, Thomas TL, Britten RJ, Davidson EH Dev. Biol Akhurst RJ (Shott RJ) Lee JJ, Britten RJ, Davidson EH Regulation of the relative abundances of mRNAs in hepatoma and liver. Birnie GD, Jacobs H, Shott R, Wilkes PR Post-transcriptional control of messenger abundance. Birnie GD, Balmain A, Jacobs H, Shott R, Wilkes PR, Paul J
