Our laboratory focuses on understanding mechanisms of cancer progression and developing clinical interventions. Our goals are to 1) uncover novel mechanisms of tumorigenesis and metastasis, 2) identify biomarkers that prognosticate disease progression or predict treatment response and 3) collaborate with industry to develop new therapies for the prevention and treatment of cancer progression.
Research
Our work in melanoma integrates current knowledge of genomic drivers with studies of the small GTPase ARF6, which controls critical cellular functions such as vesicular trafficking, cytoskeletal rearrangements, cell-cell adhesive interactions, motility, invadopodia, tumor microvesicle shedding and exosome generation. Through our studies of ARF6, we hope to illuminate how small GTPases potentiate signaling from classic oncogenic pathways such as WNT/b-catenin, RAS, BRAF/MAPK, and PI3K/AKT. In addition, we are probing the role of ARF6 in the tumor inflammatory microenvironment, as ARF6 is known to be critical for inflammatory cytokine signaling leading to vascular leak, edema, and end-organ damage in sepsis, arthritis, and retinopathy. Tumor-intrinsic inflammatory signaling has been linked to cancer progression and may represent a mechanism by which ARF6 promotes tumor growth, invasion, metastasis and perhaps tumor immune evasion.
We use a variety of in vitro and in vivo approaches to study cancer progression, including genetically-engineered mouse models, xenografts, cell culture, microscopy, biochemical, molecular biological, and genomic approaches. With clinical expertise in Anatomic and Molecular Pathology, trainees have access to mentored skill development by Dr. Grossmann in gross and microscopic morphologic assessment of in vivo tumor model systems.
View our recent article about melanoma spreading without tumor growth.
Members
Allie Harris Grossmann, MD, PhD
Assistant Professor
Division of Anatomic Pathology
Department of Pathology
University of Utah
Office Phone: (801) 213-4217
Email Address: allie.grossmann@hsc.utah.edu
Specialties: Melanoma and Cutaneous Oncology, Molecular Genetic Pathology, Pathology, Anatomical
Fellowship: University of Utah, Department of Pathology, ARUP Laboratories
Residency: University of Utah, ARUP Laboratories
Medical School: Oregon Health Sciences University
Roger Wolff, PhD
Senior Scientist, Lab Director
Coulson Rich
Lab Technician
Yinshen Wee
Postdoctoral Research Associate
Junhua Wang
Graduate Research Assistant
Publications
- Kircher DA, Trombetti KA, Silvis MR, Parkman GL, Fischer GM, Angel SN, Stehn CM, Strain SC, Grossmann AH, Duffy KL, Boucher KM, McMahon M, Davies MA, Mendoza MC, VanBrocklin MW, Holmen SL (2019). AKT1E17K Activates Focal Adhesion Kinase and Promotes Melanoma Brain Metastasis. Mol Cancer Res, 17(9), 1787-1800.
- Yoo JH, Brady SW, Acosta-Alvarez L, Rogers A, Peng J, Sorensen LK, Wolff RK, Mleynek T, Shin D, Rich CP, Kircher DA, Bild A, Odelberg SJ, Li DY, Holmen SL, Grossmann AH (2019). The Small GTPase ARF6 Activates PI3K in Melanoma to Induce a Prometastatic State. Cancer Res, 79(11), 2892-2908.
- Ekiz HA, Huffaker TB, Grossmann AH, Stephens WZ, Williams MA, Round JL, OConnell RM (2019). MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers. JCI Insight, 4(6).
- Grossmann AH, Zhao H, Jenkins N, Zhu W, Richards JR, Yoo JH, Winter JM, Rich B, Mleynek TM, Li DY, Odelberg SJ (2016). The small GTPase ARF6 regulates protein trafficking to control cellular function during development and in disease. Small GTPases, 10(1), 1-12.
- Barrott JJ, Illum BE, Jin H, Hedberg ML, Wang Y, Grossmann A, Haldar M, Capecchi MR, Jones KB (2018). Paracrine osteoprotegerin and β-catenin stabilization support synovial sarcomagenesis in periosteal cells. J Clin Invest, 28(1), 207-18.
- Yang H, Kircher DA, Kim KH, Grossmann AH, VanBrocklin MW, Holmen SL, Robinson JP (2017). Activated MEK cooperates with Cdkn2a and Pten loss to promote the development and maintenance of melanoma. Oncogene, 36(27), 3842-3851.
- Yoo JH, Shi DS, Grossmann AH, Sorensen LK, Tong Z, Mleynek TM, Rogers A, Zhu W, Richards JR, Winter JM, Zhu J, Dunn C, Bajji A, Shenderovich M, Mueller AL, Woodman SE, Harbour JW, Thomas KR, Odelberg SJ, Ostanin K, Li DY (2016). ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma. Cancer Cell, 29(6), 889-904.
- Cho JH, Robinson JP, Arave RA, Burnett WJ, Kircher DA, Chen G, Davies MA, Grossmann AH, VanBrocklin MW, McMahon M, Holmen SL (2015). AKT1 Activation Promotes Development of Melanoma Metastases. Cell Rep, 13(5), 898-905.