Research
My primary research interests lie in neuro-oncology, and I currently work as a PhD candidate in the Brain Tumor Immunotherapy Program at Duke University. My past experiences include leading an effort to expand a Phase I trial of peptide vaccination in glioblastoma currently underway at Duke University, NC, USA for patients in Scotland. I completed an academic foundation internship in the UK and following this, I continued my surgical residency while also undertaking a MSc program evaluating novel surgical practices which I completed with distinction. I have continued to develop into my role as a physician-scientist and received an early career researcher grant from the Scottish Imaging Network. I was also appointed as an Honorary Clinical Lecturer at the University of Dundee, the institution where I undertook my internship. Since joining Duke, I have used these skills to support the team in developing investigational new drug applications. I have also helped to design multiple surgical window of opportunity trials in glioblastoma patients on which I am a named sub investigator, and also received the Paul and Lauren Ghaffari graduate oncology research fellowship award for my pre-clinical work.
Ongoing Research Support
NCT05634707: FLIRT: Evaluation of Fluoxetine and Cytotoxic Lysosomal Stress in Glioma
Role: Sub-Investigator of ongoing clinical trial & protocol design
NCT04937413: PESKE: The PCSK9i Inhibitor Evolocumab - a Surgical Trial of Pharmacodynamics and Kinetics Evaluation
Role: Sub-Investigator of ongoing clinical trial & protocol design
NCT04903795: BRiTE: Bispecific T Cell Engager BRiTE for Patients with Grade IV Malignant Glioma
Role: Sub-Investigator of planned clinical trial
Positions and Scientific Appointments
08/2021-current, Duke University: Biomedical Engineering PhD Candidate
10/2020-current, University of Dundee: Honorary Clinical Lecturer
10/2020-07/2021, Duke University Medical Center: Research Scholar
08/2018-09/2020, National Health Service, Cardiff, UK: Surgical Resident
08/2016-08/2020, National Health Service, Dundee, UK: Academic Intern (medicine and surgery)
Honors
2023 Preparing Future Faculty Fellow, Duke University
2023 BME Outstanding Teaching Assistant Award, Duke University
2023 Paul and Lauren Ghaffari Graduate Oncology Research Fellowship, Duke University
2020 Postdoctoral and Early Career Researcher Exchange award, Scottish Imaging Network
2018 Best oral poster presentation in session, Association of Surgeons of Great Britain and Ireland
2017 Best poster prize in healthcare work undertaken by postgraduates, Royal College of Physicians of Edinburgh
Other Experience and Professional Memberships
General Medical Council, UK
Royal College of Surgeons, England, UK
Congress of Neurological Surgeons, USA
Society of Neuro-Oncology, USA
Society for Immunotherapy of Cancer, USA
Research Projects
My research experience includes both clinical and pre-clinical research, investigating how to best optimize current approaches undertaken in the hospital environment, while exploring novel pre-clinical strategies for treating malignant brain tumors
Evaluating novel mechanisms of drug delivery across the blood-brain barrier (BBB)
As a core component of my pre-clinical PhD research, I have been developing a novel mechanism for drug delivery into the CNS, by using stimulated T cells which can cross the BBB with macromolecules (such as antibody-based therapies) bound to their surface. I presented my initial findings at the annual meeting of the Society for Neuro-Oncology in 2021 and continue to refine the process by which T cells are stimulated, in order to best traverse the BBB
Overview of proposed drug-T cell hitchhiking mechanism. Brain Bi-specific T cell Engager (BRiTE) therapy links tumor EGFRvIII to CD3ε on T cells. EGFRvIII-targeting BRiTE accesses the central nervous system (CNS) on the surface of activated T cells
Oral Presentations
Enhancing T cell mediated delivery of immunotherapy to tumors of the central nervous system. Singh K, Foster MW, Hotchkiss KM, Snyder DJ, Khasraw M, Sampson JH. Preston Robert Tisch Brain Tumor Center Annual Retreat. June 2022 – Durham, NC, USA
Poster Abstracts
EXTH-98. Enhancing T cell trafficking of CD3-engaging immunotherapy to tumors of the central nervous system. Singh K, Foster MW, Hotchkiss KM, Snyder DJ, Khasraw M, Sampson JH. Neuro-Oncology, Volume 24, Issue Supplement 7, November 2022, Page vii232. Presented at the 27th annual meeting of the Society for Neuro-Oncology 2022.
EXTH-82. T cell hitchhiking as a mechanism of drug delivery to the brain. Singh K, Gedeon PC, Schaller T, Snyder DJ, Khasraw M, Sampson JH. Neuro-oncology, Volume 23, Issue Supplement 6, November 2021, Page vi182. Presented at the 26th annual meeting of the Society for Neuro-Oncology 2021.
Abstract 4061: Systemic autologous lymphocyte transfer can enhance tumor-infiltrating lymphocyte infiltration in glioblastoma and license co-stimulatory immunotherapy. Singh K, Hotchkiss KM, Moelker E, Archer GE, Sampson JH, Khasraw M. Cancer Research, Volume 83, 7_Supplement, April 2023, Page 4061-4061. Presented at American Association for Cancer Research Annual Meeting 2023. DOI: 10.1158/1538-7445.AM2023-406
Clinical Trials
Translating new therapies to the bedside is a core strength of the Sampson lab at Duke. During my time at Duke, I have presented the launch of a trial studying a novel bi-specific therapy targeting EGFRvIII in Glioblastoma as well as providing support for the FDA IND regulatory process. I have also assisted in summarizing data and presentation of previous trials using vaccination against antigens in glioblastoma such as Cytomegalovirus
Publications
Correcting the drug development paradigm for glioblastoma requires serial tissue sampling. Singh K, Hotchkiss KM, Parney IF, De Groot J, Sahebjam S, Sanai N, Platten M, Galanis E, Lim M, Wen PY, Minniti G, Colman H, Cloughesy TF, Mehta MP, Geurts M, Arrillaga-Romany I, Desjardins A, Tanner K, Short S, Arons D, Duke E, Wick W, Bagley SJ, Ashley DM, Kumthekar P, Verhaak R, Chalmers AJ, Patel AP, Watts C, Fecci PE, Batchelor TT, Weller M, Vogelbaum MA, Preusser M, Berger MS, Khasraw M. Nature Medicine. July 24, 2023. DOI: 10.1038/s41591-023-02464-8
Poster Abstracts
TPS2076. A phase 0/surgical window-of-opportunity study in progress, evaluating evolocumab in patients with high-grade glioma or glioblastoma. Singh K, Foster MW, Miller EZ, Gregory S, Weinhold KJ, Ashley DM, Desjardins A, Low JT, Peters KB, Severance EK, Jaggers D, Friedman HS, Johnson MO, Friedman AH, Keir ST, Herndon II JE, Li CY, Fecci PE, Sampson JH, Khasraw M. Journal of Clinical Oncology 40, no. 16_suppl (June 01, 2022) TPS2076-TPS2076. Presented at the 2022 ASCO annual meeting. American Society of Clinical Oncology 2022.
IMMU-05. A phase I study in progress of hEGFRvIII-CD3 bi-scFv (BRiTE) in patients with WHO grade IV malignant glioma. Singh K, Hotchkiss K, Gedeon P, Schaller T, Herndon J, Archer G, Sampson J, Khasraw M. Neuro-Oncology Advances, Volume 3, Issue Supplement 4, October 2021, Page iv5. Presented at 1st annual conference on CNS Clinical Trials. Society for Neuro-Oncology 2021
IMMU-04. Vaccinating against novel cytomegalovirus antigens in glioblastoma using a peptide vaccine in combination with Temozolomide. Hotchkiss K, Singh K, Batich K, Archer G, Norberg P, Desjardins A, Friedman H, Johnson M, Peters K, Khasraw M, Ashley D, Reap E, Sampson J. Neuro-Oncology Advances, Volume 3, Issue Supplement 4, October 2021, Page iv5. Presented at 1st annual conference on CNS Clinical Trials. Society for Neuro-Oncology 2021
Exploring the potential for photodynamic therapy to intra-operatively eradicate high-grade glioma
Laser light in malignant brain tumors has been used in conjunction with photosensitizing drugs to both guide surgical resection (Photodynamic Diagnosis (PDD)) and to also enhance the extent of tumor destruction (Photodynamic Therapy (PDT)). Photosensitizing drugs given pre-operatively are taken up by rapidly dividing cells, resulting in fluorescence on exposure to low visible wavelength (blue) light (PDD) or generate cytotoxic singlet oxygen species upon exposure to high visible wavelength (red) light (PDT). PDT potentially offers benefit for patients with Glioblastoma Multiforme (GBM) where it’s highly invasive & heterogeneous nature makes complete resection impossible. I presented my findings as a conference paper at the Society of Photo-Optical Instrumentation Engineers at their international world congress in 2019. I also presented a poster relating to a retrospective analysis of PDT treatment in Dundee at the European Association of Neuro-Oncology in 2018
Conference Papers
Determining an in vitro dose-response relationship of photodynamic therapy with first and second-generation photosensitizers for high grade tumors. Singh K, Baptista-Hon, Hewitt M, Kouli O, Hossain-Ibrahim K, Hales T. Conference paper presented at 17th International Photodynamic Association World Congress. August 2019 – Boston, USA. Proc. SPIE 110706E. DOI: 10.1117/12.2527574
Poster Abstracts
P01.142 Comparing outcomes in Glioblastoma Multiforme patients undergoing photodynamic therapy with a second-generation photosensitiser vs 5-Aminolevulinic Acid: A single site retrospective analysis. Singh K, Kouli O, Kanodia A, Goodman C, Eadie E, Ibbotson S, et al. Oral Poster presented at European Association of Neuro-Oncology Conference 2018 – Stockholm, Sweden. P01.142 Neuro-Oncology. 2018;20(suppl_3):iii265-iii. DOI: 10.1093/neuonc/noy139.184
Using 3D volumetric analysis of intracranial aneurysms to stratify risk of rupture
This exploratory pilot study evaluated the feasibility of using 3D software analysis to measure the volume of unruptured intracranial aneurysms and whether this could potentially provide added insight into interventional decision making. A retrospective analysis of the departmental neurovascular database was performed to identify unruptured intracranial aneurysms which subsequently required treatment. Interval imaging was evaluated using 3D volumetric analysis to determine volume change. The rate of change in single axis measurement and volume were compared to determine whether there was a uniform relationship. I presented my findings at the Society of British Neurosurgeons meeting in April 2021
Poster Abstracts
3D Volumetric Analysis of unruptured intracranial Middle Cerebral Artery aneurysm: A potential new modality to help guide interventional decision-making. Singh K, Vemaraju R, Jones E, Tumelty B, Mattar G, Van Beijnum J, Hossain-Ibrahim K, Galea J. Oral presentation at Society of British Neurosurgeons Spring Meeting. April 2021
Book Chapters
Chapter 9. Drug testing: From bench to bedside. Singh K, Sampson JH, Gedeon PC Translational Surgery. Elsevier 2023. Pages 43-51. DOI: 10.1016/B978-0-323-90300-4.00090-2
Reviews of Literature
Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma. Singh K, Batich KA, Wen PY, Tan AC, Bagley SJ, Lim M, Platten M, Colman H, Ashley DM, Chang SM, Rahman R, Galanis E, Mansouri A, Puduvalli V, Reardon DA, Sahebjam S, Sampson JH, Simes J, Berry DA, Zadeh G, Cloughesy TF, Mehta MP, Piantadosi S, Weller M, Heimberger AB, Khasraw M. Clin Cancer Res September 24 2021 DOI: 10.1158/1078-0432.CCR-21-2681
Enhancing T cell Chemotaxis and Infiltration in Glioblastoma. Singh K, Hotchkiss KM, Wilkinson DS, Mohan AA, Mohan AA, Cook SL, Sampson JH. Cancers (Basel). October 26 2021 doi: 10.3390/cancers13215367.
For whom the T cells troll? Bispecific T-cell engagers in glioblastoma. Singh K, Hotchkiss KM, Mohan AA, Reedy JL, Sampson JH, Khasraw M. J Immunother Cancer. November 2021. doi: 10.1136/jitc-2021-003679
Targeting Immunometabolism in Glioblastoma. Mohan AA, Tomaszewski WH, Haskell-Mendoza AP, Hotchkiss KM, Singh K, Reedy JL, Fecci PE, Sampson JH, Khasraw M. Frontiers in Oncology. 16 June 2021. DOI: 10.3389/fonc.2021.696402
Quality Improvement and retrospective analysis of clinical processes
As part of my work during my time as a practicing clinician, I sought to re-structure and improve the delivery of patient care. This led me to publish several times on improving various clinical processes such as admission, consenting and timing of surgeries. For this work I received an award for best oral poster presentation (for work on time of surgery as it relates to clinical outcomes). These are:
Published Papers
Endovascular and Surgical Obliteration Rates of Spinal Dural Arteriovenous Fistulae. Singh K, Zaben M, Manivannan S, van Beijnum J, Galea J, Zilani G. British Journal of Neurosurgery. 2022. DOI: 10.1080/02688697.2022.2123891
Improving the surgical consenting process for patients with acute hip fractures: a pilot quality improvement project. Singh K, Assaf A, Bayley M, Gillespie G. Patient Safety in Surgery. 2020 14:26. DOI: 10.1186/s13037-020-00252-8
Improving access to Early Intervention in Psychosis (EIP): the 2-week wait for cancer comes to psychosis. Singh K, Ghazi F, White R, et al. BMJ Open Quality. 2018 7:e000190. DOI: 10.1136/bmjoq-2017-000190
Does time of surgery influence the rate of false-negative appendectomies? A retrospective observational study of 274 patients. Singh K, Wilson SJM, Coats M. Patient Safety in Surgery. 2018 12:33. DOI: 10.1186/s13037-018-0180-2
Complete List of Publications on Google Scholar