Research Summary

I am an academic neuro-oncologist involved in clinical care, clinical research and teaching. I have extensive experience as well as formal training in clinical trial development, implementation, and analysis, including investigator-initiated, sponsored, and multi-institutional consortium and cooperative group studies testing new treatments and treatment combinations in gliomas.

I am a Co-Associate Director of the Clinical Core for the new UCSF (P01) Program Project Grant to integrate advances in physiologic and metabolic imaging with tissue biomarkers in order to optimize the management of patients with glioblastoma (GBM). I am a co-investigator in all of the current neuro-oncology therapeutic trials, as well as in several non-therapeutic studies in the areas of diagnosis, epidemiology, and quality of life. In addition, I am the principal investigator at UCSF for six active protocols.

I am study chair for a single-institution investigator-initiated study treating newly-diagnosed, subtotally resected low-grade gliomas with chemotherapy, everolimus alone or in combination with temozolomide; the treatment is selected based on molecular parameters of the patient’s tumor. This study incorporates both imaging and molecular objectives, in collaboration with colleagues from the BTRC. I am also the PI of a phase I dose-escalation study in collaboration with Memorial Sloan-Kettering, combining bevacizumab (an anti-VEGF antibody) with hypofractionated stereotactic radiation in recurrent malignant glioma. In addition to anti-tumor properties, it is thought that bevacizumab has some radio-protective properties, which may allow the stereotactic radiation dose to be escalated higher than would otherwise be tolerated. Another study is a multi-center, randomized phase II study from the ALLIANCE. It randomizes patients between three arms: an autologous heat-shock protein vaccine followed by bevacizumab at recurrence, an autologous heat-shock protein vaccine in combination with bevacizumab, or bevacizumab alone. An additional multi-center study tests a checkpoint inhibitor, MEDI4736, in combination with radiation in patients with newly-diagnosed GBMs that are MGMT unmethylated, or in combination with bevacizumab in patients with recurrent, bevacizumab-refractory GBMs.

In addition to these clinical trials, we have an ongoing longitudinal study assessing quality of life in patients with malignant gliomas undergoing initial therapy, for which I am coordinating analysis.

Education

California Institute of Technology (Caltech), Pasadena, CA, B.S., 1995, Chemistry, With Honor
University of California, San Francisco, M.D., 2002, Medicine
University of California, Berkeley, M.P.H., 2001, Health Policy and Mgmt
St. Mary’s Medical Center, San Francisco, 06/03, Intern, Internal Medicine
University of California, San Francisco, 06/06, Resident, Neurology
Memorial Sloan-Kettering Cancer Center, 06/08, Fellow, Neuro-oncology

Honors & Awards

  • 1999
    Nomination for “An Outstanding Lecture” UCSF Class of 2001
  • 2000
    University Fellowship, UC-Berkeley
  • 2000
    Award for “An Outstanding Lecture” UCSF Class of 2002
  • 2001
    UCSF Class of 1966 Scholarship
  • 2003
    Intern of the Year, St. Mary’s Medical Center
  • 2008
    ASCO Foundation Merit Award
  • 2009
    Awarded a fellowship to the 2nd Annual Clinical Trials Methods Course in Neurology, in Vail, Colorado, August 17-23, 2009; the course is sponsored by NINDS

Selected Publications

  1. Mellinghoff IK, Penas-Prado M, Peters KB, Burris HA, Maher EA, Janku F, Cote GM, de la Fuente MI, Clarke JL, Ellingson BM, Chun S, Young RJ, Liu H, Choe S, Lu M, Le K, Hassan I, Steelman L, Pandya SS, Cloughesy TF, Wen PY Vorasidenib, a dual inhibitor of mutant IDH1/2, in recurrent or progressive glioma; Results of a first-in-human Phase I trial.  View on PubMed
  2. Yu Y, Villanueva-Meyer J, Grimmer MR, Hilz S, Solomon DA, Choi S, Wahl M, Mazor T, Hong C, Shai A, Phillips JJ, Wainer BH, McDermott M, Haas-Kogan D, Taylor JW, Butowski N, Clarke JL, Berger MS, Molinaro AM, Chang SM, Costello JF, Oberheim Bush NA Temozolomide-induced hypermutation is associated with distant recurrence and reduced survival after high-grade transformation of low-grade IDH-mutant gliomas.  View on PubMed
  3. Mende AL, Schulte JD, Okada H, Clarke JL Current Advances in Immunotherapy for Glioblastoma.  View on PubMed
  4. Nayak L, Molinaro AM, Peters KB, Clarke JL, Jordan JT, de Groot JF, Nghiemphu PL, Kaley TJ, Colman H, McCluskey C, Gaffey S, Smith T, Cote DJ, Severgnini M, Yearley JH, Zhao Q, Blumenschein WM, Duda DG, Muzikansky A, Jain RK, Wen PY, Reardon DA Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma.  View on PubMed
  5. Schulte JD, Buerki RA, Lapointe S, Molinaro AM, Zhang Y, Villanueva-Meyer JE, Perry A, Phillips JJ, Tihan T, Bollen AW, Pekmezci M, Butowski N, Oberheim Bush NA, Taylor JW, Chang SM, Theodosopoulos P, Aghi MK, Hervey-Jumper SL, Berger MS, Solomon DA, Clarke JL Clinical, radiologic, and genetic characteristics of histone H3 K27M-mutant diffuse midline gliomas in adults.  View on PubMed
  6. Lucas CG, Gupta R, Doo P, Lee JC, Cadwell CR, Ramani B, Hofmann JW, Sloan EA, Kleinschmidt-DeMasters BK, Lee HS, Wood MD, Grafe M, Born D, Vogel H, Salamat S, Puccetti D, Scharnhorst D, Samuel D, Cooney T, Cham E, Jin LW, Khatib Z, Maher O, Chamyan G, Brathwaite C, Bannykh S, Mueller S, Kline CN, Banerjee A, Reddy A, Taylor JW, Clarke JL, Oberheim Bush NA, Butowski N, Gupta N, Auguste KI, Sun PP, Roland JL, Raffel C, Aghi MK, Theodosopoulos P, Chang E, Hervey-Jumper S, Phillips JJ, Pekmezci M, Bollen AW, Tihan T, Chang S, Berger MS, Perry A, Solomon DA Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor.  View on PubMed
  7. Autry AW, Gordon JW, Chen HY, LaFontaine M, Bok R, Van Criekinge M, Slater JB, Carvajal L, Villanueva-Meyer JE, Chang SM, Clarke JL, Lupo JM, Xu D, Larson PEZ, Vigneron DB, Li Y Characterization of serial hyperpolarized 13C metabolic imaging in patients with glioma.  View on PubMed
  8. Alcaide-Leon P, Luks TL, Lafontaine M, Lupo JM, Okada H, Clarke JL, Villanueva-Meyer JE Treatment-induced lesions in newly diagnosed glioblastoma patients undergoing chemoradiotherapy and heat-shock protein vaccine therapy.  View on PubMed
  9. Sloan EA, Cooney T, Oberheim Bush NA, Buerki R, Taylor J, Clarke JL, Torkildson J, Kline C, Reddy A, Mueller S, Banerjee A, Butowski N, Chang S, Mummaneni PV, Chou D, Tan L, Theodosopoulos P, McDermott M, Berger M, Raffel C, Gupta N, Sun PP, Li Y, Shah V, Cha S, Braunstein S, Raleigh DR, Samuel D, Scharnhorst D, Fata C, Guo H, Moes G, Kim JYH, Koschmann C, Van Ziffle J, Onodera C, Devine P, Grenert JP, Lee JC, Pekmezci M, Phillips JJ, Tihan T, Bollen AW, Perry A, Solomon DA Recurrent non-canonical histone H3 mutations in spinal cord diffuse gliomas.  View on PubMed
  10. Chapman CH, Hara JH, Molinaro AM, Clarke JL, Oberheim Bush NA, Taylor JW, Butowski NA, Chang SM, Fogh SE, Sneed PK, Nakamura JL, Raleigh DR, Braunstein SE Reirradiation of recurrent high-grade glioma and development of prognostic scores for progression and survival.  View on PubMed
  11. Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, Wang AC, Ellingson BM, Rytlewski JA, Sanders CM, Kawaguchi ES, Du L, Li G, Yong WH, Gaffey SC, Cohen AL, Mellinghoff IK, Lee EQ, Reardon DA, O'Brien BJ, Butowski NA, Nghiemphu PL, Clarke JL, Arrillaga-Romany IC, Colman H, Kaley TJ, de Groot JF, Liau LM, Wen PY, Prins RM Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.  View on PubMed
  12. Morrison MA, Hess CP, Clarke JL, Butowski N, Chang SM, Molinaro AM, Lupo JM Risk factors of radiotherapy-induced cerebral microbleeds and serial analysis of their size compared with white matter changes: A 7T MRI study in 113 adult patients with brain tumors.  View on PubMed
  13. Stiner RK, Clarke JL, Sinha N, Chan J, Letourneau JM, Niemasik EE, Rabbitt JE, Chang SM, Butowski NA, Prados MD, Rosen MP Attitudes toward fertility and fertility preservation in women with glioma.  View on PubMed
  14. Taylor JW, Parikh M, Phillips JJ, James CD, Molinaro AM, Butowski NA, Clarke JL, Oberheim-Bush NA, Chang SM, Berger MS, Prados M Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma.  View on PubMed
  15. Pekmezci M, Villanueva-Meyer JE, Goode B, Van Ziffle J, Onodera C, Grenert JP, Bastian BC, Chamyan G, Maher OM, Khatib Z, Kleinschmidt-DeMasters BK, Samuel D, Mueller S, Banerjee A, Clarke JL, Cooney T, Torkildson J, Gupta N, Theodosopoulos P, Chang EF, Berger M, Bollen AW, Perry A, Tihan T, Solomon DA The genetic landscape of ganglioglioma.  View on PubMed
  16. Hayes J, Yu Y, Jalbert LE, Mazor T, Jones LE, Wood MD, Walsh KM, Bengtsson H, Hong C, Oberndorfer S, Roetzer T, Smirnov IV, Clarke JL, Aghi MK, Chang SM, Nelson SJ, Woehrer A, Phillips JJ, Solomon DA, Costello JF Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas.  View on PubMed
  17. Leeper HE, Acquaye AA, Bell S, Clarke JL, Forst D, Laack NN, Link MJ, Taylor JW, Armstrong TS Survivorship care planning in neuro-oncology.  View on PubMed
  18. Byron SA, Tran NL, Halperin RF, Phillips JJ, Kuhn JG, de Groot JF, Colman H, Ligon KL, Wen PY, Cloughesy TF, Mellinghoff IK, Butowski NA, Taylor JW, Clarke JL, Chang SM, Berger MS, Molinaro AM, Maggiora GM, Peng S, Nasser S, Liang WS, Trent JM, Berens ME, Carpten JD, Craig DW, Prados MD Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma.  View on PubMed
  19. Wahl M, Chang SM, Phillips JJ, Molinaro AM, Costello JF, Mazor T, Alexandrescu S, Lupo JM, Nelson SJ, Berger M, Prados M, Taylor JW, Butowski N, Clarke JL, Haas-Kogan D Probing the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in gliomas: A phase 2 study of everolimus for recurrent adult low-grade gliomas.  View on PubMed
  20. Clarke JL, Molinaro AM, Cabrera JR, DeSilva AA, Rabbitt JE, Prey J, Drummond DC, Kim J, Noble C, Fitzgerald JB, Chang SM, Butowski NA, Taylor JW, Park JW, Prados MD A phase 1 trial of intravenous liposomal irinotecan in patients with recurrent high-grade glioma.  View on PubMed

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