Discovery to improve the lives of brain tumor patients
Discovery to improve the lives of brain tumor patients
THE KIM LABORATORY
The Brain Tumor Center
Siteman Cancer Center/Washington University School of Medicine
Department of Neurological Surgery
The problem of glioblastoma
Glioblastoma is the most common malignant primary brain tumor in adults. Despite aggressive surgical resection, chemotherapy, and radiation therapy, this disease remains challenging with no cure. We are interested in the molecular mechanisms that control key features of glioblastoma biology. The long-term goal of my laboratory is to leverage these insights for the rational design of novel strategies against this formidable disease.
GENETICS
Our laboratory is interested in developing new strategies to accurately profile patient tumors, including multisector and region-specific approaches, utilizing single cell techniques. We are also focused on establishing new experimental model systems using canonical tumor mutations.
EPIGENETICS
Therapy resistance is predominantly defined by epigenetic changes in tumor cells. Glioblastoma stem-like cells represent a dynamic and treatment-resistant cell state influenced by cell-intrinsic and -extrinsic cues. Our laboratory is interested in finding ways to disrupt the epigenetic state that defines these tumor-initiating cells. We are pursuing a variety of approaches, including high-throughput screening, pharmacology, biochemistry, genetics, and material engineering, to accomplish this goal.
METABOLISM
Cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+), which has a well-known role in oxidation-reduction reactions and is an essential component of signaling pathways as a co-factor for NAD+-dependent enzymes. The rate-limiting enzyme in NAD+ synthesis, NAMPT, is highly expressed in glioblastoma tumors. How the regulation of this enzyme interfaces with NAD+-dependent signal transduction networks remains poorly understood in glioblastoma.
LASER THERAPY
Laser therapy, also laser interstitial thermal therapy (LITT), is a minimally invasive tool used by neurosurgeons to kill tumor cells. We have established a mouse laser therapy system to examine the ability of LITT to locally disrupt the blood-brain barrier and augment drug delivery. We are also interested in how LITT changes the tumor immune microenvironment.
Our Team
Albert H. Kim, MD, PhD
Principal Investigator
Director, Brain Tumor Center
Diane Mao, MD
Lab Manager
Loren Beck
Lab Technician
Ryan Cleary, MD
Post-doctoral Fellow
Neurosurgical resident
Rowland Han, MD
Post-doctoral Fellow
Neurosurgical resident
Timothy Woodiwiss, MD
Post-doctoral Fellow
Neurosurgical resident, U Iowa
Yiwei Fu, MD
Post-doctoral Fellow
Hao Chen
PhD Student
Patrick DeSouza
MD-PhD Student
Colin McCornack
MD-PhD Student
Sangami Pugazenthi
Medical Student
David Mok
Bioinformatician
Markus Anzaldua-Campos
Undergraduate Student
Andrew Hwang
Undergraduate Student
Will Leidig
Undergraduate Student
Yoon Shin
Undergraduate Student
Alumni
Undergraduate Students
Alice Turski (2012-2014). Received 2013 Summer Undergraduate Research Fellowship to work in my laboratory.
John Finlay (Summer 2015).
Simon Gunter (2015-2016).
Ross Buchman (Summer 2019).
Alicia Yang (2020-2022)
Day Steed (Summer 2022)
Braxton Sizemore (2021-2023)
Graduate Students
Tatenda Mahlokozera (2020). PhD thesis, MD-PhD program.
Patrick Desouza (2023). PhD thesis, MD-PhD program.
Hao Chen (2023). PhD thesis, Neuroscience program.
Medical Students
Sam Sun (2013-2016). Received the Alpha Omega Alpha Award (2013) and American Brain Tumor Association Summer Fellowship (2014) to work in my lab.
Ishita Chen (Summer 2013).
Diane Aum (2014-2016). Received the David Silbert Summer Research Fellowship to work in my laboratory.
Ramin Lalezari (2014-2016).
David Dadey (2016-2017).
Ioana Flores (2017).
Mounica Pataru (2016-2019). Awarded a NREF Summer Research Fellowship.
Rukayat Taiwo (2017-2019). Awarded a HHMI Medical Fellowship
Post-doctoral Fellows
Amit Gujar, PhD (2012-2017). Currently a Staff Scientist in Roel Verhaak Lab, Jackson Laboratories, CT.
Peter Sylvester, MD (2013-2017). Resident in Neurological Surgery, Washington University.
Ananth Vellimana, MD (2014-2018). Resident in Neurological Surgery, Washington University.
Ashwin Kamath, MD (2014-2018). Resident in Neurological Surgery, Washington University.
Zohny Zohny, MD (2014-2017). Currently a Fellow in Neurological Surgery, Saint Louis University.
Thomas Beaumont, MD (2014-2016).
Rory Murphy, MD (2013-2016).
Santhi Pondugula, PhD (2014-2017).
Brendan Fong, MD (2017-2019)
Afshin Salehi, MD (2017-2020)
Dan Hafez, MD, PhD (2019-2021)
Devi Annamalai, PhD (2016-2020)
Bhuvic Patel, MD (2019-2022)
Satoka Shidoh (2021-2023)
Rui Sun (2020-2023)
Publications
2023
1. Bowman-Kirigin JA, Desai R, Saunders BT, Wang AZ, Schaettler MO, Liu CJ, Livingstone AJ, Kobayashi DK, Durai V, Kretzer NM, Zipfel GJ, Leuthardt EC, Osbun JW, Chicoine MR, Kim AH, Murphy KM, Johanns TM, Zinselmeyer BH, Dunn GP. The Conventional Dendritic Cell 1 Subset Primes CD8+ T Cells and Traffics Tumor Antigen to Drive Antitumor Immunity in the Brain. Cancer Immunol Res. 2023 Jan 3;11(1):20-37. doi: 10.1158/2326-6066.CIR-22-0098. PMID: 36409838.
2. Coxon AT, Desai R, Patel PR, Vellimana AK, Willie JT, Dowling JL, Leuthardt EC, Kim AH, Johanns TM, Siegel BA, Dunn GP. A pilot study of lymphoscintigraphy with tracer injection into the human brain. J Cereb Blood Flow Metab. 2023 Mar 30:271678X231160891. doi: 10.1177/0271678X231160891. Epub ahead of print. PMID: 36994857.
3. Chan M, Tatter S, Chiang V, Fecci P, Strowd R, Prabhu S, Hadjipanayis C, Kirkpatrick J, Sun D, Sinicrope K, Mohammadi AM, Sevak P, Abram S, Kim AH, Leuthardt E, Chao S, Phillips J, Lacroix M, Williams B, Placantonakis D, Silverman J, Baumgartner J, Piccioni D, Laxton A. Efficacy of laser interstitial thermal therapy for biopsy-proven radiation necrosis in radiographically recurrent brain metastases. Neurooncol Adv. 2023 Mar 28;5(1):vdad031. doi: 10.1093/noajnl/vdad031. PMID: 37114245; PMCID: PMC10129388.
4. Sun R, Han R, McCornack C, Khan S, Tabor GT, Chen Y, Hou J, Jiang H, Schoch KM, Mao DD, Cleary R, Yang A, Liu Q, Luo J, Petti A, Miller TM, Ulrich JD, Holtzman DM, Kim AH. TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma. Sci Adv. 2023 May 12;9(19):eade3559. doi: 10.1126/sciadv.ade3559. Epub 2023 May 12. PMID: 37172094; PMCID: PMC10181199.
5. McCornack C, Woodiwiss T, Hardi A, Yano H, Kim AH. The function of histone methylation and acetylation regulators in GBM pathophysiology. Front Oncol. 2023 May 2;13:1144184. doi: 10.3389/fonc.2023.1144184. PMID: 37205197; PMCID: PMC10185819.
6. Han RH, Johanns TM, Roberts KF, Tao Y, Luo J, Ye Z, Sun P, Blum J, Lin TH, Song SK, Kim AH. Diffusion basis spectrum imaging as an adjunct to conventional MRI leads to earlier diagnosis of high-grade glioma tumor progression versus treatment effect. Neurooncol Adv. 2023 Apr 19;5(1):vdad050. doi: 10.1093/noajnl/vdad050. PMID: 37215950; PMCID: PMC10195207.
7. Aghi MK, Brastianos PK, Kim AH, Kalkanis SN, Tonn JC. Introduction. Update on brain metastases. Neurosurg Focus. 2023 Aug;55(2):E1. doi: 10.3171/2023.6.FOCUS23343. PMID: 37527676.
8. Ghosh S, Johanns TM, Chheda MG, Liu E, Butt O, Abraham C, Badiyan S, Huang Y, DeNardo D, Kim AH, Hallahan D, Thotala D, Huang J. A pilot phase Ib study to evaluate tadalafil to overcome immunosuppression during chemoradiotherapy for IDH-wild-type glioblastoma. Neurooncol Adv. 2023 Jul 19;5(1):vdad088. doi: 10.1093/noajnl/vdad088. PMID: 37554225; PMCID: PMC10406429.
2022
1 Yang PH, Tao Y, Luo J, Paturu M, Lu HC, Ramkissoon S, Heusel JW, Leuthardt EC, Chicoine MR, Dowling JL, Dunn GP, Duncavage E, Dahiya S, Chattherjee AR, Kim AH. Multivariate analysis of associations between clinical sequencing and outcome in glioblastoma. Neurooncol Adv. 2022 Jan 10;4(1):vdac002. doi: 10.1093/noajnl/vdac002. PMID: 35156038; PMCID: PMC8826782.
2. Hwang H, Huang J, Khaddour K, Butt OH, Ansstas G, Chen J, Katumba RG, Kim AH, Leuthardt EC, Campian JL. Prolonged response of recurrent IDH-wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab. CNS Oncol. 2022 Jan 19:CNS81. doi: 10.2217/cns-2021-0013. Epub ahead of print. PMID: 35043686.
3. Patel B, Desai R, Pugazenthi S, Butt OH, Huang J, Kim AH. Identification and Management of Aggressive Meningiomas. Front Oncol. 2022 Mar 23;12:851758. doi: 10.3389/fonc.2022.851758. PMID: 35402234; PMCID: PMC8984123.
4. Johnson GW, Han RH, Smyth MD, Leuthardt EC, Kim AH. Laser Interstitial Thermal Therapy in Grade 2/3 IDH1/2 Mutant Gliomas: A Preliminary Report and Literature Review. Curr Oncol. 2022 Apr 8;29(4):2550-2563. doi: 10.3390/curroncol29040209. PMID: 35448183; PMCID: PMC9028957.
5. Wang AZ, Bowman-Kirigin JA, Desai R, Kang LI, Patel PR, Patel B, Khan SM, Bender D, Marlin MC, Liu J, Osbun JW, Leuthardt EC, Chicoine MR, Dacey RG Jr, Zipfel GJ, Kim AH, DeNardo DG, Petti AA, Dunn GP. Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response. Genome Med. 2022 May 10;14(1):49. doi: 10.1186/s13073-022-01051-9. PMID: 35534852; PMCID: PMC9088131.
6. de Groot JF, Kim AH, Prabhu S, Rao G, Laxton AW, Fecci PE, O'Brien BJ, Sloan A, Chiang V, Tatter SB, Mohammadi AM, Placantonakis DG, Strowd RE, Chen C, Hadjipanayis C, Khasraw M, Sun D, Piccioni D, Sinicrope KD, Campian JL, Kurz SC, Williams B, Smith K, Tovar-Spinoza Z, Leuthardt EC. Efficacy of laser interstitial thermal therapy (LITT) for newly diagnosed and recurrent IDH wild-type glioblastoma. Neurooncol Adv. 2022 Apr 6;4(1):vdac040. doi: 10.1093/noajnl/vdac040. PMID: 35611270; PMCID: PMC9122789.
7. Mao DD, Cleary RT, Gujar A, Mahlokozera T, Kim AH. CDC20 regulates sensitivity to chemotherapy and radiation in glioblastoma stem cells. PLoS One. 2022 Jun 23;17(6):e0270251. doi: 10.1371/journal.pone.0270251. PMID: 35737702; PMCID: PMC9223386.
8. Grabowski MM, Srinivasan ES, Vaios EJ, Sankey EW, Otvos B, Krivosheya D, Scott A, Olufawo M, Ma J, Fomchenko EI, Herndon JE, Kim AH, Chiang VL, Chen CC, Leuthardt EC, Barnett GH, Kirkpatrick JP, Mohammadi AM, Fecci PE. Combination laser interstitial thermal therapy plus stereotactic radiotherapy increases time to progression for biopsy-proven recurrent brain metastases. Neurooncol Adv. 2022 Jun 2;4(1):vdac086. doi: 10.1093/noajnl/vdac086. PMID: 35795470; PMCID: PMC9248774.
9. Cross KA, Desai R, Vellimana A, Liu Y, Rich K, Zipfel G, Dacey R, Chicoine M, Klatt-Cromwell C, McJunkin J, Pipkorn P, Schneider JS, Silverstein J, Kim AH. Surgery for Pituitary Tumor Apoplexy Is Associated with Rapid Headache and Cranial Nerve Improvement. Curr Oncol. 2022 Jul 12;29(7):4914-4922. doi: 10.3390/curroncol29070390. PMID: 35877250; PMCID: PMC9319222.
10. Broestl L, Warrington NM, Grandison L, Abou-Antoun T, Tung O, Shenoy S, Tallman MM, Rhee G, Yang W, Sponagel J, Yang L, Kfoury-Beaumont N, Hill CM, Qanni SA, Mao DD, Kim AH, Stewart SA, Venere M, Luo J, Rubin JB. Gonadal sex patterns p21-induced cellular senescence in mouse and human glioblastoma. Commun Biol. 2022 Aug 2;5(1):781. doi: 10.1038/s42003-022-03743-9. PMID: 35918603; PMCID: PMC9345919.
11. Sun R, Kim AH. The multifaceted mechanisms of malignant glioblastoma progression and clinical implications. Cancer Metastasis Rev. 2022 Aug 3. doi: 10.1007/s10555-022-10051-5. Epub ahead of print. PMID: 35920986.
12. Cui Zhou D, Jayasinghe RG, Chen S, Herndon JM, Iglesia MD, Navale P, Wendl MC, Caravan W, Sato K, Storrs E, Mo CK, Liu J, Southard-Smith AN, Wu Y, Naser Al Deen N, Baer JM, Fulton RS, Wyczalkowski MA, Liu R, Fronick CC, Fulton LA, Shinkle A, Thammavong L, Zhu H, Sun H, Wang LB, Li Y, Zuo C, McMichael JF, Davies SR, Appelbaum EL, Robbins KJ, Chasnoff SE, Yang X, Reeb AN, Oh C, Serasanambati M, Lal P, Varghese R, Mashl JR, Ponce J, Terekhanova NV, Yao L, Wang F, Chen L, Schnaubelt M, Lu RJ, Schwarz JK, Puram SV, Kim AH, Song SK, Shoghi KI, Lau KS, Ju T, Chen K, Chatterjee D, Hawkins WG, Zhang H, Achilefu S, Chheda MG, Oh ST, Gillanders WE, Chen F, DeNardo DG, Fields RC, Ding L. Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer. Nat Genet. 2022 Aug 22. doi: 10.1038/s41588-022-01157-1. Epub ahead of print. PMID: 35995947.
13. Li YD, Coxon AT, Huang J, Abraham CD, Dowling JL, Leuthardt EC, Dunn GP, Kim AH, Dacey RG, Zipfel GJ, Evans J, Filiput EA, Chicoine MR. Neoadjuvant stereotactic radiosurgery for brain metastases: a new paradigm. Neurosurg Focus. 2022 Nov;53(5):E8. doi: 10.3171/2022.8.FOCUS22367. PMID: 36321291.
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2015
2014
2013
Other notable studies
WE ARE ACTIVELY SEEKING TALENTED GRADUATE STUDENTS AND POSTDOCTORAL FELLOWS.
Please contact Us if you have any questions about the laboratory.
The Kim Laboratory
Department of Neurological Surgery