Professor Mariaelena Pierobon

MD, MPH

School of Medicine and Population Health

Professor of Applied Molecular Oncology

m.pierobon@sheffield.ac.uk

DU37, D Floor, The Medical School

Full contact details

Professor Mariaelena Pierobon
School of Medicine and Population Health
DU37, D Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX

Qualifications: Medical Degree Universita’ degli Studi di Padova (Padova, Italy)
Master’s in Public Health George Mason University (Fairfax, VA, USA)

Research interests

My research programme focuses on the molecular mechanisms that shape tumour progression and therapeutic resistance, with the aim of identifying vulnerabilities that can be used to improve treatment options for patients with advanced and hard‑to‑treat malignancies. I integrate mechanistic cancer biology, functional proteomics, and multi‑omic approaches to define how oncogenic signalling networks malfunction and how these alterations can be used to inform therapeutic strategies.

A consistent feature of my programme is its translational orientation. Findings generated in the laboratory are evaluated in clinical settings through biomarker‑driven patient stratification, functional profiling of patient samples, and studies that connect molecular mechanisms with therapeutic response. This approach has supported clinical investigations across several cancer types and has contributed to work on treatment resistance, adaptive signalling, and precision‑guided therapy selection.

Research themes include:

Overcoming therapeutic resistance in breast cancer: defining mechanisms of CDK4/6 inhibitor resistance and developing strategies to counter them in HR+/HER2‑ disease.
Decoding oncogenic protein dysfunction: mapping non-canonical functions, protein-protein interactions, and isoform dynamics of dysregulated oncogenic proteins, with a focus on how overexpressed oncoproteins lose canonical activity and adopt scaffolding roles in alternative cellular compartments, and how these behaviours shift therapeutic strategies from inhibition to targeted degradation.
Preventing lineage plasticity: identifying windows of vulnerability that can be targeted to block phenotypic switching and tumour evolution.
Integrating functional signalling analysis into precision medicine: using proteomic and signalling network profiling of patient samples within multi-omic frameworks to guide clinical decision making and improve patient stratification and therapeutic selection.

Publications

Journal articles

Drizyte-Miller K, Engstrom LD, Klomp JA, Stalnecker CA, Stamey AG, Taylor KE, Roach MK, Robb R, Waters LM, Calinisan A , Degan S et al (2025) Combination of the MTA-Cooperative PRMT5 Inhibitor BMS-986504 and KRAS Inhibitors Is an Effective Treatment Strategy for MTAP -Deleted KRAS -Mutant Pancreatic Cancer. Cancer Research, 85(18), 3540-3557.
Prasad D, Baldelli E, Blais EM, Davis J, El Gazzah E, Mueller C, Gomeiz A, Ibrahim A, Newrekar AV, Corgiat BA , Dunetz R et al (2024) Functional activation of the AKT-mTOR signalling axis in a real-world metastatic breast cancer cohort. British Journal of Cancer, 131(9), 1543-1554.
Klomp JE, Diehl JN, Klomp JA, Edwards AC, Yang R, Morales AJ, Taylor KE, Drizyte-Miller K, Bryant KL, Schaefer A , Johnson JL et al (2024) Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer. Science, 384(6700).
Blas PE, Rodriguez ESR, Williams HL, Levin MK, Bell JSK, Pierobon M, Barrett AS, Petricoin EF & O'Shaughnessy JA (2024) Targeting HER2/HER3 co‐mutations in metastatic breast cancer: Case reports of exceptional responders to trastuzumab and pertuzumab therapy. Cancer Reports, 7(3).
Hunt AL, Bateman NW, Barakat W, Makohon-Moore SC, Abulez T, Driscoll JA, Schaaf JP, Hood BL, Conrads KA, Zhou M , Calvert V et al (2024) Mapping three-dimensional intratumor proteomic heterogeneity in uterine serous carcinoma by multiregion microsampling. Clinical Proteomics, 21(1).
Schaefer A, Hodge RG, Zhang H, Hobbs GA, Dilly J, Huynh MV, Goodwin CM, Zhang F, Diehl JN, Pierobon M , Baldelli E et al (2023) RHOA^L57Vdrives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling. Science Signaling, 16(816).
Pierobon M & Petricoin EF (2023) Functional proteomic analysis, a missing piece for understanding clonal evolution and cooperation in the tissue microecology. Expert Review of Molecular Diagnostics, 23(12), 1057-1059.
Wood K, Nussbaum D, Martz C, Waters A, Barrera A, Rutter J, Cerda-Smith C, Stewart A, Wu C, Cakir M , Levandowski C et al (2023) Mediator Kinase Inhibition Impedes Transcriptional Plasticity and Prevents Resistance to ERK/MAPK-Targeted Therapy in KRAS-Mutant Cancers.
Goodwin CM, Waters AM, Klomp JE, Javaid S, Bryant KL, Stalnecker CA, Drizyte-Miller K, Papke B, Yang R, Amparo AM , Ozkan-Dagliyan I et al (2023) Combination Therapies with CDK4/6 Inhibitors to Treat KRAS- Mutant Pancreatic Cancer. Cancer Research, 83(1), 141-157.
Soltis AR, Bateman NW, Liu J, Nguyen T, Franks TJ, Zhang X, Dalgard CL, Viollet C, Somiari S, Yan C , Zeman K et al (2022) Proteogenomic analysis of lung adenocarcinoma reveals tumor heterogeneity, survival determinants, and therapeutically relevant pathways. Cell Reports Medicine, 3(11), 100819-100819.
Baldelli E, Mandarano M, Bellezza G, Petricoin EF & Pierobon M (2022) Analysis of neuroendocrine clones in NSCLCs using an immuno-guided laser-capture microdissection-based approach. Cell Reports Methods, 2(8), 100271-100271.
Huynh MV, Hobbs GA, Schaefer A, Pierobon M, Carey LM, Diehl JN, DeLiberty JM, Thurman RD, Cooke AR, Goodwin CM , Cook JH et al (2022) Functional and biological heterogeneity of KRAS ^Q61 mutations. Science Signaling, 15(746).
Javaid S, Schaefer A, Goodwin CM, Nguyen VV, Massey FL, Pierobon M, Gambrell-Sanders D, Waters AM, Lambert KN, Diehl JN , Hobbs GA et al (2022) Concurrent Inhibition of ERK and Farnesyltransferase Suppresses the Growth of HRAS Mutant Head and Neck Squamous Cell Carcinoma. Molecular Cancer Therapeutics, 21(5), 762-774.
Stalnecker CA, Grover KR, Edwards AC, Coleman MF, Yang R, DeLiberty JM, Papke B, Goodwin CM, Pierobon M, Petricoin EF , Gautam P et al (2022) Concurrent Inhibition of IGF1R and ERK Increases Pancreatic Cancer Sensitivity to Autophagy Inhibitors. Cancer Research, 82(4), 586-598.
Naeem A, Harish V, Coste S, Parasido EM, Choudhry MU, Kromer LF, Ihemelandu C, Petricoin EF, Pierobon M, Noon MS , Yenugonda VM et al (2022) Regulation of Chemosensitivity in Human Medulloblastoma Cells by p53 and the PI3 Kinase Signaling Pathway. Molecular Cancer Research, 20(1), 114-126.
Pierobon M, Robert NJ, Northfelt DW, Jahanzeb M, Wong S, Hodge KA, Baldelli E, Aldrich J, Craig DW, Liotta LA , Avramovic S et al (2022) Multi‐omic molecular profiling guide’s efficacious treatment selection in refractory metastatic breast cancer: a prospective phase II clinical trial. Molecular Oncology, 16(1), 104-115.
Klomp JE, Lee YS, Goodwin CM, Papke B, Klomp JA, Waters AM, Stalnecker CA, DeLiberty JM, Drizyte-Miller K, Yang R , Diehl JN et al (2021) CHK1 protects oncogenic KRAS-expressing cells from DNA damage and is a target for pancreatic cancer treatment. Cell Reports, 37(9), 110060-110060.
Diehl JN, Klomp JE, Snare KR, Hibshman PS, Blake DR, Kaiser ZD, Gilbert TSK, Baldelli E, Pierobon M, Papke B , Yang R et al (2021) The KRAS-regulated kinome identifies WEE1 and ERK coinhibition as a potential therapeutic strategy in KRAS-mutant pancreatic cancer. Journal of Biological Chemistry, 297(5), 101335-101335.
Baldelli E, Hodge KA, Bellezza G, Shah NJ, Gambara G, Sidoni A, Mandarano M, Ruhunusiri C, Dunetz B, Abu-Khalaf M , Wulfkuhle J et al (2021) PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine. Journal for ImmunoTherapy of Cancer, 9(10), e002179-e002179.
Codrich M, Dalla E, Mio C, Antoniali G, Malfatti MC, Marzinotto S, Pierobon M, Baldelli E, Di Loreto C, Damante G , Terrosu G et al (2021) Integrated multi-omics analyses on patient-derived CRC organoids highlight altered molecular pathways in colorectal cancer progression involving PTEN. Journal of Experimental & Clinical Cancer Research, 40(1).
Hunt AL, Bateman NW, Barakat W, Makohon-Moore S, Hood BL, Conrads KA, Zhou M, Calvert V, Pierobon M, Loffredo J , Litzi TJ et al (2021) Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens. iScience, 24(7), 102757-102757.
Zhao X, Kim I, Kallakury B, Chahine JJ, Iwama E, Pierobon M, Petricoin E, McCutcheon JN, Zhang Y, Umemura S , Chen V et al (2021) Acquired small cell lung cancer resistance to Chk1 inhibitors involves Wee1 up‐regulation. Molecular Oncology, 15(4), 1130-1145.
Ozkan-Dagliyan I, Diehl JN, George SD, Schaefer A, Papke B, Klotz-Noack K, Waters AM, Goodwin CM, Gautam P, Pierobon M , Peng S et al (2020) Low-Dose Vertical Inhibition of the RAF-MEK-ERK Cascade Causes Apoptotic Death of KRAS Mutant Cancers. Cell Reports, 31(11), 107764-107764.
Hunt AL, Pierobon M, Baldelli E, Oliver J, Mitchell D, Gist G, Bateman NW, Larry Maxwell G, Petricoin EF & Conrads TP (2020) The impact of ultraviolet- and infrared-based laser microdissection technology on phosphoprotein detection in the laser microdissection-reverse phase protein array workflow. Clinical Proteomics, 17(1).
Zhang H, Schaefer A, Wang Y, Hodge RG, Blake DR, Diehl JN, Papageorge AG, Stachler MD, Liao J, Zhou J , Wu Z et al (2020) Gain-of-Function RHOA Mutations Promote Focal Adhesion Kinase Activation and Dependency in Diffuse Gastric Cancer. Cancer Discovery, 10(2), 288-305.
Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, Sudhakar N, Bowcut V, Baer BR, Ballard JA , Burkard MR et al (2020) The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients. Cancer Discovery, 10(1), 54-71.
Hobbs GA, Baker NM, Miermont AM, Thurman RD, Pierobon M, Tran TH, Anderson AO, Waters AM, Diehl JN, Papke B , Hodge RG et al (2020) Atypical KRASG12R Mutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer. Cancer Discovery, 10(1), 104-123.
Tew BY, Legendre C, Schroeder MA, Triche T, Gooden GC, Huang Y, Butry L, Ma DJ, Johnson K, Martinez RA , Pierobon M et al (2020) Patient-derived xenografts of central nervous system metastasis reveal expansion of aggressive minor clones. Neuro-Oncology, 22(1), 70-83.
Ponnusamy S, Asemota S, Schwartzberg LS, Guestini F, McNamara KM, Pierobon M, Font-Tello A, Qiu X, Xie Y, Rao PK , Thiyagarajan T et al (2019) Androgen Receptor Is a Non-canonical Inhibitor of Wild-Type and Mutant Estrogen Receptors in Hormone Receptor-Positive Breast Cancers. iScience, 21, 341-358.
Parasido E, Avetian GS, Naeem A, Graham G, Pishvaian M, Glasgow E, Mudambi S, Lee Y, Ihemelandu C, Choudhry M , Peran I et al (2019) The Sustained Induction of c-MYC Drives Nab-Paclitaxel Resistance in Primary Pancreatic Ductal Carcinoma Cells. Molecular Cancer Research, 17(9), 1815-1827.
Nadella S, Burks J, Huber M, Wang J, Cao H, Kallakury B, Tucker RD, Boca SM, Jermusyck A, Collins I , Vietsch EE et al (2019) Endogenous Gastrin Collaborates With Mutant KRAS in Pancreatic Carcinogenesis. Pancreas, 48(7), 894-903.
Bryant KL, Stalnecker CA, Zeitouni D, Klomp JE, Peng S, Tikunov AP, Gunda V, Pierobon M, Waters AM, George SD , Tomar G et al (2019) Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer. Nature Medicine, 25(4), 628-640.
Pierobon M, Petricoin EF & Wulfkuhle JD (2018) Phosphoprotein-based drug target activation mapping for precision oncology: a view to the future. Expert Review of Proteomics, 15(11), 851-853.
Younossi ZM, Karrar A, Pierobon M, Birerdinc A, Stepanova M, Abdelatif D, Younoszai Z, Jeffers T, Felix S, Jeiran K , Hodge A et al (2018) An exploratory study examining how nano-liquid chromatography–mass spectrometry and phosphoproteomics can differentiate patients with advanced fibrosis and higher percentage collagen in non-alcoholic fatty liver disease. BMC Medicine, 16(1).
Eke I, Makinde AY, Aryankalayil MJ, Sandfort V, Palayoor ST, Rath BH, Liotta L, Pierobon M, Petricoin EF, Brown MF , Stommel JM et al (2018) Exploiting Radiation-Induced Signaling to Increase the Susceptibility of Resistant Cancer Cells to Targeted Drugs: AKT and mTOR Inhibitors as an Example. Molecular Cancer Therapeutics, 17(2), 355-367.
Pierobon M, Ramos C, Wong S, Hodge KA, Aldrich J, Byron S, Anthony SP, Robert NJ, Northfelt DW, Jahanzeb M , Vocila L et al (2017) Enrichment of PI3K-AKT–mTOR Pathway Activation in Hepatic Metastases from Breast Cancer. Clinical Cancer Research, 23(16), 4919-4928.
Sereni MI, Baldelli E, Gambara G, Ravaggi A, Hodge KA, Alberts DS, Guillen-Rodriguez JM, Dong T, Memo M, Odicino F , Angioli R et al (2017) Kinase-driven metabolic signalling as a predictor of response to carboplatin–paclitaxel adjuvant treatment in advanced ovarian cancers. British Journal of Cancer, 117(4), 494-502.
Varghese RS, Zuo Y, Zhao Y, Zhang Y-W, Jablonski SA, Pierobon M, Petricoin EF, Ressom HW & Weiner LM (2017) Protein network construction using reverse phase protein array data. Methods, 124, 89-99.
Ludovini V, Chiari R, Tomassoni L, Antonini C, Baldelli E, Baglivo S, Siggillino A, Tofanetti FR, Bellezza G, Hodge KA , Petricoin E et al (2017) Reverse phase protein array (RPPA) combined with computational analysis to unravel relevant prognostic factors in non- small cell lung cancer (NSCLC): a pilot study. Oncotarget, 8(47), 83343-83353.
Parasido EM, Silvestri A, Canzonieri V, Belluco C, Diodoro MG, Milione M, Melotti F, De Maria R, Liotta L, Petricoin EF & Pierobon M (2017) Protein drug target activation homogeneity in the face of intra-tumor heterogeneity: implications for precision medicine. Oncotarget, 8(30), 48534-48544.
Pin E, Stratton S, Belluco C, Liotta L, Nagle R, Hodge KA, Deng J, Dong T, Baldelli E, Petricoin E & Pierobon M (2016) A pilot study exploring the molecular architecture of the tumor microenvironment in human prostate cancer using laser capture microdissection and reverse phase protein microarray. Molecular Oncology, 10(10), 1585-1594.
Marmiroli S, Fabbro D, Miyata Y, Pierobon M & Ruzzene M (2015) Phosphorylation, Signaling, and Cancer: Targets and Targeting. BioMed Research International, 2015, 1-3.
Nussbaum DP, Martz CA, Waters AM, Barrera A, Liu A, Rutter JC, Cerda-Smith CG, Stewart AE, Wu C, Cakir M , Levandowski CB et al () Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers. npj Precision Oncology, 8(1).
Bateman NW, Abulez T, Soltis AR, McPherson A, Choi S, Garsed DW, Pandey A, Tian C, Hood BL, Conrads KA , Teng P-N et al () Author Correction: Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities. npj Precision Oncology, 8(1).
Bateman NW, Abulez T, Soltis AR, McPherson A, Choi S, Garsed DW, Pandey A, Tian C, Hood BL, Conrads KA , Teng P-N et al () Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities. npj Precision Oncology, 8(1).
Anderson T, Herrera D, Mireku F, Barner K, Kokkinakis A, Dao H, Webber A, Merida AD, Gallo T & Pierobon M () Geographical Variation in Social Determinants of Female Breast Cancer Mortality Across US Counties. JAMA Network Open, 6(9), e2333618-e2333618.
Dunn B, Pierobon M & Wei Q () Automated Classification of Lung Cancer Subtypes Using Deep Learning and CT-Scan Based Radiomic Analysis. Bioengineering, 10(6), 690-690.
Abu-Khalaf MM, Alex Hodge K, Hatzis C, Baldelli E, El Gazzah E, Valdes F, Sikov WM, Mita MM, Denduluri N, Murphy R , Zelterman D et al () AKT/mTOR signaling modulates resistance to endocrine therapy and CDK4/6 inhibition in metastatic breast cancers. npj Precision Oncology, 7(1).
Le Roux Ö, Pershing NLK, Kaltenbrun E, Newman NJ, Everitt JI, Baldelli E, Pierobon M, Petricoin EF & Counter CM () Genetically manipulating endogenous Kras levels and oncogenic mutations in vivo influences tissue patterning of murine tumorigenesis. eLife, 11.
Lin KH, Rutter JC, Xie A, Killarney ST, Vaganay C, Benaksas C, Ling F, Sodaro G, Meslin P-A, Bassil CF , Fenouille N et al () P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia. Nature Cancer, 3(7), 837-851.
Baldelli E, El Gazzah E, Moran JC, Hodge KA, Manojlovic Z, Bassiouni R, Carpten JD, Ludovini V, Baglivo S, Crinò L , Bianconi F et al () Wild-Type KRAS Allele Effects on Druggable Targets in KRAS Mutant Lung Adenocarcinomas. Genes, 12(9), 1402-1402.
Baldelli E, Subramanian M, Alsubaie AM, Oldaker G, Emelianenko M, El Gazzah E, Baglivo S, Hodge KA, Bianconi F, Ludovini V , Crino’ L et al () Heterogeneous Off-Target Effects of Ultra-Low Dose Dimethyl Sulfoxide (DMSO) on Targetable Signaling Events in Lung Cancer In Vitro Models. International Journal of Molecular Sciences, 22(6), 2819-2819.
Rao G, Pierobon M, Kim I-K, Hsu W-H, Deng J, Moon Y-W, Petricoin EF, Zhang Y-W, Wang Y & Giaccone G () Inhibition of AKT1 signaling promotes invasion and metastasis of non-small cell lung cancer cells with K-RAS or EGFR mutations. Scientific Reports, 7(1).

Book chapters

Pierobon M, Wulfkuhle J, Liotta LA & Petricoin III EF (2019) Utilization of Proteomic Technologies for Precision Oncology Applications, Cancer Treatment and Research (pp. 171-187). Springer International Publishing
Baldelli E, Calvert V, Hodge A, VanMeter A, Petricoin EF & Pierobon M (2017) Reverse Phase Protein Microarrays, Methods in Molecular Biology (pp. 149-169). Springer New York

School of Medicine and Population Health

School of Medicine and Population Health

Professor Mariaelena Pierobon

Journal articles

Book chapters

Links