Neuropathology Unit

The Neuropathology Unit performs both independent and collaborative research related to the characterization and understanding of central nervous system (CNS) disorders. As a part of its mission, the Neuropathology Unit collects and maintains neurosurgical tissue for the Surgical Neurology Branch (SNB) biorepository. This annotated tissue is available for SNB investigators and is also accessible for collaborative research across the NINDS and the NIH.

Under the supervision of Dr. Cimino, the Unit’s primary research efforts are in molecular neuro-oncology, focusing on identifying and characterizing genetic drivers of IDH-wildtype and IDH-mutant adult diffuse gliomas, utilizing both human tissue and genetically engineered mouse models. Most recently, projects have concentrated on identifying and characterizing prognostic somatic copy number alterations (SCNAs), as well as uncovering the biology of novel SCNA-related oncogenes and tumor suppressors in IDH-wildtype glioblastoma and IDH-mutant astrocytoma. An additional active area of investigation includes characterizing developmentally regulated transcription factors in IDH-mutant and 1p/19q-codeleted oligodendroglioma.

Research collaborations occur both within the SNB and NINDS, along with outside academic institutions. Recent collaborative research efforts with Dr. Cimino as co-investigator involve several aspects of brain tumor biology, including characterizing mouse models of fusion-driven brain tumors, investigating mechanisms of dormancy for metastatic carcinoma to the brain, characterizing the response of microtubule inhibiting agents in a mouse model of glioblastoma, developing handheld confocal instruments for improved glioma resection, and validating new techniques of epigenetic testing in glioblastoma. Current collaborative investigations also include applying whole-genome methylation profiling to CNS tumor classification and risk-stratification. The Unit is also available for Neuropathology-related services, such as histopathology-based collaborative research.

Downloadable SNB Biorepository Research Requisition Forms:

Lab Members:

NPU

 


IDH Composite

IDH composite

scRNASeq 

scRNAseq

 

Select Publications:

2022 

Cimino PJ, Ketchum C, Turakulov R, Singh O, Abdullaev Z, Giannini C, Pytel P, Lopez GY, Colman H, Nasrallah MP, Santi M, Fernandes IL, Nirschl J, Dahiya S, Neill S, Solomon D, Perez E, Capper D, Mani H, Caccamo D, Ball M, Badruddoja M, Chkheidze R, Camelo-Piragua S, Fullmer J, Alexandrescu S, Yeaney G, Eberhart C, Martinez-Lage M, Chen J, Zach L, Kleinschmidt-DeMasters BK, Hefti M, Lopes MB, Nuechterlein N, Horbinski C, Rodriguez FJ, Quezado M, Pratt D, Aldape K (2022)
Expanded analysis of high-grade astrocytoma with piloid features identifies an epigenetically and clinically distinct subtype associated with neurofibromatosis type 1.
Acta Neuropathol, PubMed ID: 36271929

Pattwell SS, Arora S, Nuechterlein N, Zager M, Loeb KR, Cimino PJ, Holland NC, Reche-Ley N, Bolouri H, Almiron Bonnin DA, Szulzewsky F, Phadnis VV, Ozawa T, Wagner MJ, Haffner MC, Cao J, Shendure J, Holland EC (2022)
Oncogenic role of a developmentally regulated NTRK2 splice variant.
Sci Adv, 8:eabo6789. PubMed ID: 36206341

Wu Z, Rajan S, Chung HJ, Raffeld M, Panneer Selvam P, Schweizer L, Perry A, Samuel D, Giannini C, Ragunathan A, Frosch MP, Marshall MS, Boué DR, Donev K, Neill SG, Fernandes I, Resnick A, Rood B, Cummings TJ, Buckley AF, Szymanski L, Neto OLA, Zach L, Colman H, Cheshier S, Ziskin J, Tyagi M, Capper D, Abdullaev Z, Cimino PJ, Quezado M, Pratt D, Aldape K (2022)
Molecular and clinicopathologic characteristics of gliomas with EP300::BCOR fusions.
Acta Neuropathol, PubMed ID: 36201019

Szulzewsky F, Arora S, Arakaki AKS, Sievers P, Almiron Bonnin DA, Paddison PJ, Sahm F, Cimino PJ, Gujral TS, Holland EC (2022)
Both YAP1-MAML2 and constitutively active YAP1 drive the formation of tumors that resemble NF2 mutant meningiomas in mice.
Genes Dev, PubMed ID: 36008139

Park JH, Feroze AH, Emerson SN, Mihalas AB, Keene CD, Cimino PJ, de Lomana ALG, Kannan K, Wu WJ, Turkarslan S, Baliga NS, Patel AP (2022)
A single-cell based precision medicine approach using glioblastoma patient-specific models.
NPJ Precis Oncol, 6:55. PubMed ID: 35941215

Dai J, Cimino PJ, Gouin KH, Grzelak CA, Barrett A, Lim AR, Long A, Weaver S, Saldin LT, Uzamere A, Schulte V, Clegg N, Pisarsky L, Lyden D, Bissell MJ, Knott S, Welm AL, Bielas JH, Hansen KC, Winkler F, Holland EC, Ghajar CM (2022)
Astrocytic laminin-211 drives disseminated breast tumor cell dormancy in brain.
Nat Cancer, 3:25-42. PubMed ID: 35121993

2021


Nuechterlein N, Shapiro LG, Holland EC, Cimino PJ (2021)
Machine learning modeling of genome-wide copy number alteration signatures reliably predicts IDH mutational status in adult diffuse glioma.
Acta Neuropathol Commun, 9:191. PubMed ID: 34863298

Wu SJ, Furlan SN, Mihalas AB, Kaya-Okur HS, Feroze AH, Emerson SN, Zheng Y, Carson K, Cimino PJ, Keene CD, Sarthy JF, Gottardo R, Ahmad K, Henikoff S, Patel AP (2021)
Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression.
Nat Biotechnol, 39:819-824. PubMed ID: 33846646

Nuechterlein N, Li B, Feroze A, Holland EC, Shapiro L, Haynor D, Fink J, Cimino PJ (2021)
Radiogenomic modeling predicts survival-associated prognostic groups in glioblastoma.
Neurooncol Adv, 3:vdab004. PubMed ID: 33615222

2019


Yoda RA, Marxen T, Longo L, Ene C, Wirsching HG, Keene CD, Holland EC, Cimino PJ (2019)
Mitotic Index Thresholds Do Not Predict Clinical Outcome for IDH-Mutant Astrocytoma.
J Neuropathol Exp Neurol, 78:1002-1010. PubMed ID: 31529048

Cimino PJ, Holland EC (2019)
Targeted copy number analysis outperforms histologic grading in predicting patient survival for WHO grades II/III IDH-mutant astrocytomas.
Neuro Oncol, 21:819-821. PubMed ID: 30918961

2018


Cimino PJ, McFerrin L, Wirsching HG, Arora S, Bolouri H, Rabadan R, Weller M, Holland EC (2018)
Copy number profiling across glioblastoma populations has implications for clinical trial design.
Neuro Oncol, 20:1368-1373. PubMed ID: 29982740

Puchalski RB, Shah N, Miller J, Dalley R, Nomura SR, Yoon JG, Smith KA, Lankerovich M, Bertagnolli D, Bickley K, Boe AF, Brouner K, Butler S, Caldejon S, Chapin M, Datta S, Dee N, Desta T, Dolbeare T, Dotson N, Ebbert A, Feng D, Feng X, Fisher M, Gee G, Goldy J, Gourley L, Gregor BW, Gu G, Hejazinia N, Hohmann J, Hothi P, Howard R, Joines K, Kriedberg A, Kuan L, Lau C, Lee F, Lee H, Lemon T, Long F, Mastan N, Mott E, Murthy C, Ngo K, Olson E, Reding M, Riley Z, Rosen D, Sandman D, Shapovalova N, Slaughterbeck CR, Sodt A, Stockdale G, Szafer A, Wakeman W, Wohnoutka PE, White SJ, Marsh D, Rostomily RC, Ng L, Dang C, Jones A, Keogh B, Gittleman HR, Barnholtz-Sloan JS, Cimino PJ, Uppin MS, Keene CD, Farrokhi FR, Lathia JD, Berens ME, Iavarone A, Bernard A, Lein E, Phillips JW, Rostad SW, Cobbs C, Hawrylycz MJ, Foltz GD (2018)
An anatomic transcriptional atlas of human glioblastoma.
Science, 360:660-663. PubMed ID: 29748285

Cimino PJ, Kim Y, Wu HJ, Alexander J, Wirsching HG, Szulzewsky F, Pitter K, Ozawa T, Wang J, Vazquez J, Arora S, Rabadan R, Levine R, Michor F, Holland EC (2018)
Increased HOXA5 expression provides a selective advantage for gain of whole chromosome 7 in IDH wild-type glioblastoma.
Genes Dev, 32:512-523. PubMed ID: 29632085

2017


Cimino PJ, Zager M, McFerrin L, Wirsching HG, Bolouri H, Hentschel B, von Deimling A, Jones D, Reifenberger G, Weller M, Holland EC (2017)
Multidimensional scaling of diffuse gliomas: application to the 2016 World Health Organization classification system with prognostically relevant molecular subtype discovery.
Acta Neuropathol Commun, 5:39. PubMed ID: 28532485