Molecular Pathology Research Laboratory

Research Program Overview

The Molecular Pathology Research Laboratory, Genetics and Molecular Pathology has a broad program incorporating several local, national and international projects focussing on discovery and characterisation of genetic diseases, and generation and use of genomics information. Projects encompass research, diagnostic and clinical aspects, and incorporate basic research and translation for clinically relevant diagnostic, prognostic and therapeutic benefit to patients, families, and society.

Current Research Projects

Australian Familial Haematological Conditions Study (AFHCS) - Identifying the genetic causes of predisposition to blood cancers, bone marrow failure and related conditions.
- Discovery and characterisation of known and novel blood cancer predisposition genes (somatic mutations, expanded phenotypes, mechanisms of action, early detection markers, prevention of disease onset, new therapies).
- Examining the role of the pathogenic bone marrow microenvironment and haematopoietic stem cell stress in the development of leukaemia in blood cancer predisposition.

Advancing genetic diagnosis and health by leveraging high-throughput functional assay data into existing disease-agnostic variant platforms.
- Using Multiplex assays of variant effect (MAVE) to measure the functional effect of all possible missense variants in blood cancer predisposition genes GATA2 and RUNX1 to facilitate classification of clinically relevant variants to benefit patients.

The Australian Genomic Autopsy study is a nation-wide, MRFF-funded translational research project focusing on identification of genetic variants underlying pregnancy loss, pregnancy terminations and perinatal deaths.
- We offer genomic analysis and reporting (NATA-accredited) for variants in established (OMIM-) disease genes, leading to known severe developmental disorders.
- Performing functional studies to
  - Determine the effect of novel variants in known disease genes
  - Discover and establish novel gene-disease relationships, by characterising the downstream effect of variants in candidate genes which have not yet been associated with human diseases.

Molecular Screening and Therapeutics (MoST) in Leukaemia and Lymphoma (MoST-LLy) clinical trials & immunotherapy.

Australian Genomics – “National and international networks bringing together clinicians, diagnosticians, industry, researchers, bioinformaticians, policy makers, and consumers who are united in their aim to achieve equitable and appropriate applications of genomics in healthcare”.
- VariantGrid/Shariant – variant analysis platform and rapid and efficient national and global sharing of gene variant data to facilitate patient treatment and management.
- Acute Care Genomics
- Genomic Autopsy
- MoST/MoST-LLy
- AFHCS
- CML integrative genomic analysis: clinical trials
RNA-4RD: RNA for Rare Disease – developing disease-agnostic, nationally-accessible pipelines for clinical RNA diagnostics.

Lipedema Study - discovery and characterisation of the genetics leading to markedly abnormal fat deposition in women.

Laboratory staff

Laboratory head

Professor Hamish Scott

Adjunct Professor, Centre for Cancer Biology

HB8-32, City West Campus

(08) 8302 7678

Hamish.Scott@unisa.edu.au

Team Members

Associate Professor Christopher Hahn
(Section Head, Molecular Pathology Research Laboratory)
Associate Professor Anna Brown
(Head, Molecular Oncology, SA Pathology)

Postdoctoral Research Scientists

Research and technical assistants

Students

Ms Saba Montazaribarforoushi (PhD)
Ms Jiarna Zerella (PhD)
Ms Grace Howie (Honours)

Select Recent Publications

Drazer MW, Homan CC, Yu K, Cavalcante de Andrade Silva M, McNeely KE, Pozsgai MJ, Acevedo-Mendez MG, Segal JP, Wang P, Feng J, King-Smith SL, Kim E, Korotev S, Lawrence DM, Schreiber AW, Hahn CN, Scott HS, Sood R; NISC Comparative Sequencing Program, Velloso EDRP, Brown AL, Liu PP, Godley LA (2022) Clonal hematopoiesis in patients with ANKRD26 or ETV6 germline mutations. Blood Adv. 6:4357-4359. doi:10.1182/bloodadvances.2022007211. PMID: 35537115.
Saumya E. Samaraweera, Tatjana Geukens, Debora A. Casolari, Tran Nguyen, Caitlyn Sun, Sheree Bailey, Sarah Moore, Jinghua Feng, Andreas W. Schreiber, Wendy T. Parker, Anna L. Brown, Carolyn Butcher, Peter G. Bardy, Michael Osborn, Hamish S. Scott, Dipti Talaulikar, Carolyn S. Grove, Christopher N. Hahn, Richard J. D’Andrea, David M. Ross (2022) Novel modes of MPL activation in triple-negative myeloproliferative neoplasms. Pathology S0031-3025(22)00219-7. doi:10.1016/j.pathol.2022.05.015. PMID: 36031433.
Caner Saygin, Gregory Roloff, Christopher Hahn, Rakchha Chhetri, Saar Gill, Hany Elmariah, Chetasi Talati, Emma Nunley, Guimin Gao, Aelin Kim, Michael Bishop, Satyajit Kosuri, Soma Das, Deepak Singhal, Parvathy Venugopal, Claire Homan, Anna Brown, Hamish Scott, Devendra Hiwase, and Lucy Godley (2022) Allogeneic hematopoietic stem cell transplant outcomes in adults with inherited myeloid malignancies. Blood Adv. 2022 Aug 24. doi:10.1182/bloodadvances.2022008172. PMID: 36001442.
Baranwal A, Hahn CN, Shah MV, Hiwase DK. Role of Germline Predisposition to Therapy-Related Myeloid Neoplasms. Current Hematologic Malignancy Reports (Curr Hematol Malig Rep.) 2022 Aug 20. doi: 10.1007/s11899-022-00676-2. PMID: 35986863.
Yıldız Bölükbaşı E, Karolak JA, Szafranski P, Gambin T, Matsika A, McManus S, Scott HS, Arts P, Ha T, Barnett CP, Rodgers J, Stankiewicz P (2022) Variable expressivity in a four-generation ACDMPV family with a non-coding hypermorphic SNV in trans to the frameshifting FOXF1 variant. Eur J Hum Genet. 2022 Jul 28. doi: 10.1038/s41431-022-01159-x. PMID: 35902696.
Lao L, Bourdeau I, Gagliardi L, He X, Shi W, Hao B, Tan M, Hu Y, Peng J, Coulombe B, Torpy DJ, Scott HS, Lacroix A, Luo H, Wu J (2022) ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia. Nucleic Acids Res. Jun 24;50(11):6343-6367. doi: 10.1093/nar/gkac483. PMID: 35687106.
Wu D, Bampton TJ, Scott HS, Brown A, Kassahn K, Drogemuller C, De Sousa SM, Moore D, Ha T, Chen JW, Khurana S, Torpy DJ, Radford T, Couper R, Palmer L, Coates PT (2022) The clinical and genetic features of hereditary pancreatitis in South Australia. Med J Aust. Jun 20;216(11):578-582. doi: 10.5694/mja2.51517. PMID: 35578795.
Van der Sluijs PJ, Joosten M, Alby C, Attié-Bitach T, Gilmore K, Dubourg C, Fradin M, Wang T, Kurtz-Nelson EC, Ahlers KP, Arts P, Barnett CP, Ashfaq M, Baban A, van den Born M, Borrie S, Busa T, Byrne A, Carriero M, Cesario C, Chong K, Cueto-González AM, Dempsey JC, Diderich KEM, Doherty D, Farholt S, Gerkes EH, Gorokhova S, Govaerts LCP, Gregersen PA, Hickey SE, Lefebvre M, Mari F, Martinovic J, Northrup H, O'Leary M, Parbhoo K, Patrier S, Popp B, Santos-Simarro F, Stoltenburg C, Thauvin-Robinet C, Thompson E, Vulto-van Silfhout AT, Zahir FR, Scott HS, Earl RK, Eichler EE, Vora NL, Wilnai Y, Giordano JL, Wapner RJ, Rosenfeld JA, Haak MC, Santen GWE (2022) Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort. Genet Med. Aug;24(8):1753-1760 doi: 10.1016/j.gim.2022.04.010. PMID: 35579625.
Feurstein S, Hahn CN, Mehta N, Godley LA (2022) A practical guide to interpreting germline variants that drive hematopoietic malignancies, bone marrow failure, and chronic cytopenias. Genet. Med. 24:931-954. doi: 10.1016/j.gim.2021.12.008. PMID: 35063349.
Byrne AB, Brouillard P, Sutton DL, Kazenwadel J, Montazaribarforoushi S, Secker GA, Oszmiana A, Babic M, Betterman KL, Brautigan PJ, White M, Piltz SG, Thomas PQ, Hahn CN, Rath M, Felbor U, Korenke GC, Smith CL, Wood KH, Sheppard SE, Adams DM, Kariminejad A, Helaers R, Boon LM, Revencu N, Moore L, Barnett C, Haan E, Arts P, Vikkula M, Scott HS, Harvey NL (2022) Pathogenic variants in MDFIC cause recessive central conducting lymphatic anomaly with lymphedema. Sci Transl Med. 14(634):eabm4869. doi: 10.1126/scitranslmed.abm4869. PMID: 35235341.
Kiran Tawana, Anna L. Brown, Jane Churpek. Integrating germline variant assessment into routine clinical practice for myelodysplastic syndrome and acute myeloid leukaemia: current strategies and challenges. Invited review, British Journal of Haematology 2022 Mar;196(6):1293-1310. doi: 10.1111/bjh.17855. PMID: 34658019.
Samaraweera SE, Wang PP, Li KL, Casolari DA, Feng J, Pinese M, Maung KZY, Leo PJ, Cowley MJ, Perkins K, Smith AM, Ellis J, Wee A, Hiwase DK, Scott HS, Schreiber AW, Brown AL, Deans AJ, Ross DM, Moore AS, Gonda T, Hahn CN, D'Andrea RJ. Childhood Acute Myeloid Leukemia shows a high level of germline predisposition. Blood. 2021 Dec 2;138(22):2293-2298. PMID: 34521114.
Ravindran E, Jühlen R, Vieira-Vieira CH, Ha T, Salzberg Y, Fichtman B, Luise-Becker L, Martins N, Picker-Minh S, Bessa P, Arts P, Jackson MR, Taranath A, Kamien B, Barnett C, Li N, Tarabykin V, Stoltenburg-Didinger G, Harel A, Selbach M, Dickmanns A, Fahrenkrog B, Hu H, Scott H, Kaindl AM Expanding the phenotype of NUP85 mutations beyond nephrotic syndrome to primary autosomal recessive microcephaly and Seckel syndrome spectrum disorders. Hum Mol Genet. 2021 Nov 1;30(22):2068-2081. doi: 10.1093/hmg/ddab160.PMID: 34170319.
Singhal D*, Hahn CN*, Feurstein S*, Wee LYA, Moma L, Kutyna MM, Chhetri R, Eshraghi L, Schreiber AW, Feng J, Wang PP, Babic M, Parker WT, Gao S, Moore S, Das S, Thomas D, Pattnaik S, Brown AL, D'Andrea RJ, Poplawski NK, Thomas D, Scott HS, Godley LA, Hiwase DK (2021) Targeted gene panels identify a high frequency of pathogenic germline variants in patients diagnosed with a hematological malignancy and at least one other independent cancer. Leukemia 35:3245-3256. doi: 10.1038/s41375-021-01246-w. PMID: 33850299.
Avagyan S, Brown AL To T or not to B: germline RUNX1 mutation preferences in pediatric ALL predisposition. J Clin Invest. 2021 Sep 1;131(17):e152464. PMID: 34623329.
Six KA, Gerdemann U, Brown AL, Place AE, Cantor AB, Kutny MA, Avagyan S. B-cell acute lymphoblastic leukemia in patients with germline RUNX1 mutations. Blood Adv. 2021 Aug 24;5(16):3199-3202. PMID: 34424323.
Homan CC, King-Smith SL, Lawrence DM, Arts P, Feng J, Andrews J, Armstrong M, Ha T, Dobbins J, Drazer MW, Yu K, Bödör C, Cantor A, Cazzola M, Degelman E, DiNardo CD, Duployez N, Favier R, Fröhling S, Fitzgibbon J, Klco JM, Krämer A, Kurokawa M, Lee J, Malcovati L, Morgan NV, Natsoulis G, Owen C, Patel KP, Preudhomme C, Raslova H, Rienhoff H, Ripperger T, Schulte R, Tawana K, Velloso E, Yan B, Liu P, Godley LA, Schreiber AW, Hahn CN, Scott HS, Brown AL (2021) The RUNX1 Database (RUNX1db): Establishment of an expert curated RUNX1 registry and genomics database as a public resource for familial platelet disorder with myeloid malignancy. Haematologica 2021 Jul 8. doi: 10.3324/haematol.2021.278762. PMID: 34233450.
Homan CC, Venugopal P, Arts P, Shahrin NH, Feurstein S, Rawlings L, Lawrence DM, Andrews J, King-Smith SL, Harvey NL, Brown AL, Scott HS, Hahn CN (2021) GATA2 deficiency syndrome: A decade of discovery. Hum Mutat. 42:1399-1421. doi: 10.1002/humu.24271. PMID: 34387894.
Tan NB, Pagnamenta AT, Ferla MP, Gadian J, Chung BH, Chan MC, Fung JL, Cook E, Guter S, Boschann F, Heinen A, Schallner J, Mignot C, Keren B, Whalen S, Sarret C, Mittag D, Demmer L, Stapleton R, Saida K, Matsumoto N, Miyake N, Sheffer R, Mor-Shaked H, Barnett CP, Byrne AB, Scott HS, Kraus A, Cappuccio G, Brunetti-Pierri N, Iorio R, Di Dato F, Pais LS, Yeung A, Tan TY, Taylor JC, Christodoulou J, White SM (2022) Recurrent de novomissense variants in GNB2 can cause syndromic intellectual disability. J Med Genet. 2022 May;59(5):511-516. doi: 10.1136/jmedgenet-2020-107462. PMID: 34183358.
De Angelis C, Byrne AB, Morrow R, Feng J, Ha T, Wang P, Schreiber AW, Babic M, Taranath A, Manton N, King-Smith SL, Schwarz Q, Arts P, Scott HS, Barnett C (2021) Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia. BMC Med Genomics. 2021 Feb 27;14(1):64. doi: 10.1186/s12920-021-00911-4. PMID: 33639934.