A major question we are trying to answer in my laboratory is "What is the role of the inflammatory response in tumor progression". We are studying the role of proteins that promote the migration of inflammatory cells into tissues. These "chemotactic" proteins can educate leukocytes to either stimulate or inhibit tumor progression. These factors can also stimulate the growth of the tumor and recruit blood vessels into the tumor to provide a continuous supply of nutrients to feed tumor growth. We have tested with a variety of pharmaceutical drugs that shut down the inflammatory process and alter the expression of genes that recruit inflammatory cells into the tumor microenvironment. We are also evaluating how to deliver therapies that teach the patient's leukocytes to fight the growth of the tumor and switch from a pro-tumorigenic to an anti-tumorigenic state.

My laboratory also investigates the intracellular signals that are important in the tumor microenvironment and in the pre-metastatic niche to reduce the establishment of metastatic lesions.     Recently, following basic discoveries on the pathways involved in melanoma progression, we have developed translational studies using patient-derived xenograft models to explore new therapeutic approaches for melanoma.  We recently demonstrated that combining aurora kinase A inhibitors with MDM2 antagonists markedly inhibits melanoma tumor growth, using patient derived xenograft models as well as immunocompetent mouse models.   We now plan to extend our initial studies combining Aurora Kinase and MDM2 inhibitors to evaluate an even more promising combination therapy, CDK4/6 inhibitors and MDM2 antagonists.  We develop animal models and utilize in vitro and in vivo imaging techniques to characterize the mechanism by which antagonists of cell cycle combined with reagents that enhance apoptosis may synergize to improve treatment for cancer.

 We are experienced in the characterization of leukocyte interaction with the tumor microenvironment and in identification of subsets of these cells within the tumor using FACS. Moreover, we are currently characterizing the role of a number of small molecule inhibitors that affect melanoma and breast cancer growth and metastasis using patient derived xenografts. We are also examining how certain targeted therapies enhance the anti-tumor immune response when combined with check-point inhibitors.  We have an outstanding group of collaborators and access to phenomenal infrastructure for acquiring patients, obtaining informed consent, tissue collection, patient follow-up, and access to patients in clinical trials. 

Publications

Featured publications

  1. Development of novel murine mammary imaging windows to examine wound healing effects on leukocyte trafficking in mammary tumors with intravital imaging. Sobolik T, Su YJ, Ashby W, Schaffer DK, Wells S, Wikswo JP, Zijlstra A, Richmond A (2016) Intravital 5(1): e1125562
    › Primary publication · 28243517 (PubMed) · PMC5226013 (PubMed Central)
  2. The Yin/Yan of CCL2: a minor role in neutrophil anti-tumor activity in vitro but a major role on the outgrowth of metastatic breast cancer lesions in the lung in vivo. Lavender N, Yang J, Chen SC, Sai J, Johnson CA, Owens P, Ayers GD, Richmond A (2017) BMC Cancer 17(1): 88
    › Primary publication · 28143493 (PubMed) · PMC5286656 (PubMed Central)
  3. Bortezomib augments lymphocyte stimulatory cytokine signaling in the tumor microenvironment to sustain CD8+T cell antitumor function. Pellom ST, Dudimah DF, Thounaojam MC, Uzhachenko RV, Singhal A, Richmond A, Shanker A (2017) Oncotarget 8(5): 8604-8621
    › Primary publication · 28052005 (PubMed)
  4. PI3K Inhibition Reduces Mammary Tumor Growth and Facilitates Anti-tumor Immunity and Anti-PD1 Responses. Sai J, Owens P, Novitiskiy SV, Hawkins OE, Vilgelm AE, Yang J, Sobolik-Delmaire T, Lavender N, Johnson AC, McClain C, Ayers GD, Kelley MC, Sanders M, Mayer IA, Moses HL, Boothby M, Richmond A (2016) Clin Cancer Res
    › Primary publication · 28003307 (PubMed)
  5. Epithelial NF-κB signaling promotes EGFR-driven lung carcinogenesis via macrophage recruitment. Saxon JA, Sherrill TP, Polosukhin VV, Sai J, Zaynagetdinov R, McLoed AG, Gulleman PM, Barham W, Cheng DS, Hunt RP, Gleaves LA, Richmond A, Young LR, Yull FE, Blackwell TS (2016) Oncoimmunology 5(6): e1168549
    › Primary publication · 27471643 (PubMed) · PMC4938365 (PubMed Central)
  6. Combinatorial approach to cancer immunotherapy: strength in numbers. Vilgelm AE, Johnson DB, Richmond A (2016) J Leukoc Biol 100(2): 275-90
    › Primary publication · 27256570 (PubMed)
  7. Tumor Characteristics, Genetics, Management, and the Risk of Metastasis in Uveal Melanoma. Nichols EE, Richmond A, Daniels AB (2016) Semin Ophthalmol 31(4): 304-9
    › Primary publication · 27128983 (PubMed)
  8. Disparities in Uveal Melanoma: Patient Characteristics. Nichols EE, Richmond A, Daniels AB (2016) Semin Ophthalmol 31(4): 296-303
    › Primary publication · 27128153 (PubMed)
  9. The role of NF-kB in modulating antitumor immunity. Richmond A, Yang J (2016) Oncoimmunology 5(1): e1005522
    › Primary publication · 26942050 (PubMed) · PMC4760307 (PubMed Central)
  10. Study of Chemotaxis and Cell-Cell Interactions in Cancer with Microfluidic Devices. Sai J, Rogers M, Hockemeyer K, Wikswo JP, Richmond A (2016) Methods Enzymol : 19-45
    › Primary publication · 26921940 (PubMed)

NCI CA34590; CA116021; VA Merit Award, VA Senior Career Scientist Award; U54 CA91405;P30 CA068485

Community Leaders

Contact Information

Department of Cancer Biology
Vanderbilt University School of Medicine
432 Preston Research Building
Nashville, TN 37232
USA
6153437998 (p)

No contact person provided

Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

Adaptor Proteins, Vesicular Transport Androstadienes Animals Antineoplastic Agents, Hormonal aurora kinases breast cancer CD8-Positive T-Lymphocytes Cell Growth Processes chemokines chemotaxis Diffusion Epidermal Growth Factor Estrogen Antagonists Hypoxia inflammation as a driver of tumorigenesis Kinetics Luminescent Proteins Melanocytes melanoma Melanoma, Experimental Mitogen-Activated Protein Kinase 1 NF-kB Okadaic Acid PI3K Poly (ADP-Ribose) Polymerase-1 Pregnancy Receptor, Epidermal Growth Factor Sp1 Transcription Factor translational medicine research