Alessio Giubellino, MD, PhD

Assistant Professor, Department of Laboratory Medicine and Pathology

Alessio Giubellino

Contact Info

agiubell@umn.edu

Office Phone 612-624-5407

Office Address:
C516 Mayo Memorial Bldg.

Lab Address:
MCRB 7W-6

MD, University of Turin School of Medicine, 1999

Residency in Anatomic Pathology, National Institutes of Health (NIH) – Clinical Center Laboratory of Pathology, NCI, 2016

Fellowship in Dermatopathology, University of Miami Miller School of Medicine, 2017

PhD, Experimental and Molecular Oncology, University of Pisa School of Medicine, 2014

Summary

Dr. Giubellino is an anatomic pathologist and dermatopathologist whose current research is focused on understanding the molecular mechanisms and signaling pathways in melanoma with the goal of developing predictive biomarkers and combination therapies for the disease. He employs molecular and cellular techniques and immunohistochemical analysis of tissue samples to bridge basic science and clinical medicine.

Giubellino’s research in Italy and at the National Cancer institute laid the foundation for his current studies of melanoma. With his colleagues, he investigated c-Met, a tyrosine-kinase receptor protein encoded by the MET gene. When bound by its ligand hepatocyte growth factor (HGF), c-Met activates a wide range of cellular signaling pathways including those important in cellular proliferation, motility, migration, and tissue development and invasion. Giubellino’s chief interest is the growing evidence of c-Met’s role in cancer metastasis, which can turn early-stage noninvasive in situ melanoma into a deadly disease. Although none has received FDA approval, c-Met inhibitors hold promise for arresting advanced metastasis and also minimal residual disease in which small numbers of melanoma cells with metastatic potential remain dormant in the patient following treatment.

Melanoma is very complex disease with multiple chromosomal and genetic aberrations and a cascade of cell-signaling pathways. Giubellino is developing a research program designed to identify key molecules and pathways responsible for melanoma metastasis, use the data to subclassify the disease and stratify patients, and target and disrupt metastatic networks with small-molecule drugs. He and fellow researchers have investigated the effect of c-Met kinase receptor on downstream effectors such as Grb2 and adaptors proteins, signal transduction molecules that may serve as targets for small-molecule drug disruption of the signaling network. Giubellino’s ultimate goal is to combine classical protein kinase receptor-targeted drug therapy with checkpoint blockade immunotherapy, which received FDA approval for metastatic melanoma in 2011. Molecular and cellular studies, animal testing, and human trials will determine whether the combination strategy Giubellino plans to undertake provides a therapeutic synergy that is superior to targeted therapy or immunotherapy alone.

Giubellino’s basic research investigation of metastatic melanoma networks dovetails with his clinical studies of patient samples. Results from immunohistochemical staining of tissue specimens can be correlated with results from molecular and genetic analysis, giving the dermatopathologist a more complete picture of the disease. Giubellino thinks this comprehensive approach will reveal predictive biomarkers in metastatic melanoma that can indicate whether and how a patient will respond to specific therapies, a key goal of personalized medicine. 

Research

Publications

Journal articles

  • Glinos GD, Pastar I,Giubellino A. Tomic-Canic M, Miteva M, Stone RC.Novel mevalonate kinase missense mutation in a patient with disseminated superficial actinic porokeratosis JAAD Case Reports, Vol. 4, Issue 4, p340–343
  • Fekrazad R, Sarrafzadeh A, Kalhori KA, Khan I, Arany PR, Giubellino A.  Improved Wound Remodeling Correlates with Modulated TGF-beta Expression in Skin Diabetic Wounds Following Combined Red and Infrared Photobiomodulation Treatments. Photochem Photobiol. 2018 Feb 19. doi: 10.1111/php.12914. [Epub ahead of print] PMID:29457837
  • Eber AE, Rosen A, Oberlin KE, Giubellino A, Romanelli P. Ichthyosiform Pityriasis Rubra Pilaris-Like Eruption Secondary to Ponatinib Therapy: Case Report and Literature Review Drug Saf Case Rep. 2017 Nov 14;4(1):19. doi: 10.1007/s40800-017-0055-y. PMID: 29138996 https://www.ncbi.nlm.nih.gov/pubmed/29138996
  • Billero V, LaSenna C, Romanelli M, Giubellino A, Brenes RA, Romanelli P. Primary cutaneous diffuse large B-cell lymphoma presenting as chronic non-healing ulcer. International Wound Journal 2017 Jan 24.
  • Giubellino A, Lara K, Martucci V, Huynh T, Agarwal P, Pacak K, Merino MJ. Urinary bladder paragangliomas: How immunohistochemistry can assist to identify patients with SDHB germline and somatic mutations. Am. J. Surg. Path. 2015 Nov; 39 (11): 1488-92.
  • Schovanek J, Bullova P, Tayem Y, Giubellino A, Wesley R, Lendvai N, Nölting S, Kopacek J, Frysak Z, Pommier Y, Kummar S, Pacak K. Inhibitory effect of the non-camptothecin topoisomerase I inhibitor LMP-400 on female mice models and human pheochromocytoma cells. Endocrinology. 2015 Aug 12
  • Szarek E, Ball ER, Imperiale A, Tsokos M, Faucz FR, Giubellino A, Moussallieh FM, Namer IJ, Abu-Asab M, Pacak K, Taieb D, Carney A, Stratakis CA. Carney Triad, SDH-deficient tumors, and SDHB+/- mice share abnormal mitochondria. Endocr Relat Cancer. 2015 Mar 25
  • Xekouki P, Szarek E, Bullova P, Giubellino A, Quezado M, Mastroyannis SA, Mastorakos P, Wassif CA, Raygada M, Rentia N, Dye L, Cougnoux A, Koziol D, de La Luz Sierra M, Lyssikatos C, Belyavskaya E, Malchoff C, Moline J, Eng C, Maher LJ Third, Pacak K, Lodish M, Stratakis CA. Pituitary adenoma with paraganglioma/pheochromocytoma (3PAs) and succinate dehydrogenase defects in human and mice. J Clin Endocrinol Metab. 2015 Feb 19
  • McNeil BK, Sorbellino M, Grubb RL 3rd, Apolo A, Cecchi F, Athauda G, Cohen B, Giubellino A, Simpson H, Agarwal PK, Coleman J, Getzenberg RH, Netto GJ, Shih J, Linehan WM, Pinto PA, Bottaro DP. Preliminary evaluation of urine soluble Met as a biomarker for urothelial carcinoma of the bladder. J Transl Med. 2014 Oct 21; 12:199
  • Giubellino A, Shankavaran U, Bullova P, Schovanek J, Zhang Y, Shen M, Patel N, Elkahloun A, Lee M-J, Trepel J, Ferrer M and Pacak K. High-throughput screening for the identification of new therapeutic options for metastatic pheochromocytoma and paraganglioma. PLoS One. April 2014
  • Nölting S, Giubellino A, Tayem Y, Young K, Lauseker M, Bullova P, Schovanek J, Anver M, Fliedner S, Korbonits M, Göke B, Vlotides G, Grossman A, Pacak K. Combination of 13-cis retinoic acid and lovastatin: marked anti-tumor potential in vivo in a pheochromocytoma allograft model in female athymic nude mice. Endocrinology. April 2014
  • Powers JF, Korgaonkar PG, Fliedner S, Giubellino A, Sahagian KP, Tischler AS.Cytocidal Activities of Topoisomerase 1 Inhibitors and 5-Azacytidine against Pheochromocytoma/Paraganglioma Cells in Primary Human Tumor Cultures and Mouse Cell Lines. PLoS One. 2014 Feb 7;9(2)
  • Ghayee HK, Giubellino A, Click A, Kapur P, Christie A, Xie XJ, Martucci V, Shay JW, Souza RF, Pacak K. Phospho-mTOR is not upregulated in metastatic SDHB paragangliomas. Eur J Clin Invest. 2013 Sep;43(9):970-7.
  • Giubellino A, Sourbier C, Lee MJ, Scroggins B, Bullova P, Landau M, Ying W, Neckers L, Trepel JB, Pacak K. Targeting heat shock protein 90 for the treatment of malignant pheochromocytoma. PLoS One. 2013;8(2):e56083
  • Matro J, Giubellino A, Pacak K. Current and future therapeutic approaches for metastatic pheochromocytoma and paraganglioma: focus on SDHB tumors. Horm Metab Res. 2013 Feb;45(2): 147-53
  • Giubellino A, Bullova P, Nolting S, Turkova H, Powers JF, Liu Q, Guichard S, Tischler AS, Grossman AB, Pacak K. Combined inhibition of mTORC1 and mTORC2 signaling pathway is a promising therapeutic option in inhibiting pheochromocytoma tumor growth: in vitro and in vivo studies in female athymic nude mice. Endocrinology. 2013 Feb;154(2)646-55
  • Nölting S, Garcia E, Alusi G, Giubellino A, Pacak K, Korbonits M, Grossman A. Combined blockade of signaling pathways shows marked anti-tumor potential in phaeochromocytoma cell lines. J Mol Endocrinol. 2012 Jun 19
  • Shah U, Giubellino A, Pacak K. Pheochromocytoma: implications in tumorigenesis and the actual management. Minerva Endocrinol. 2012 Jun;37(2):141-56
  • Pacak K., Sirova M, Giubellino A, Lencesova L, Csaderova L, Laukova M, Hudecova S, Krizanova O. NF- ?B inhibition significantly upregulates the norepinephrine transporter system, causes apoptosis in pheochromocytoma cell lines and prevents metastasis in an animal model. Int J Cancer. 2012 Mar 12
  • Giubellino A., Woldemichael GM, Sourbier C, Lizak MJ, Powers JF, Tischler AS, Pacak K. Characterization of of two mouse models of metastatic pheochromocytoma using bioluminescence imaging. Cancer Lett. 2012 Mar;316(1):46-52
  • Liu F, Giubellino A, Simister PC, Qian W, Giano MC, Feller SM, Bottaro DP, Burke TR Jr. Application of ring-closing metathesis to Grb2 SH3 domain-binding peptides. Biopolymers. 2011; 96(6): 780.

Book chapters

  • Elgart GW, Giubellino A – Acanthomas chapter – WHO / IARC Classification of Tumours – Pathology and Genetics of Skin Tumours, 4th Edition (in preparation – scheduled for publication in 2018)
  • Giubellino A - “Adaptor Proteins” in Encyclopedia of Cancer, Edited by Prof. Manfred Schwab Springer (invited, accepted for online publication 2012)
  • Athauda G, Cecchi F, Ito T, Giubellino A, Rabe DC, Raffensperger K, Lee Y and Donald P Bottaro - “A review of HGF biology” in Atlas of Genetics and Cytogenetics in Oncology and Haematology (Published online June 2011)
  • Giubellino A - “Grb2 signaling as a molecular target for cancer” in “Signaling mechanisms and molecular targets in cancer” Edited by Prof. Malay Chatterjee. Cambridge University Press (invited, accepted for publication 2010)

Clinical

Board Certifications

Anatomic Pathology, Dermatopathology