Bio

Clinical Focus


  • Hematology/Oncology

Academic Appointments


Honors & Awards


  • St. Baldrick's Fellowship Award, St. Baldrick's Foundation (2019-2021)
  • Alpha Omega Alpha Honor Society, Alpha Omega Alpha (2018)
  • Tashia and John Morgridge Endowed Postdoctoral Fellowship, Children's Health Research Institute, Stanford University (2017-2019)
  • Young Scientist Award, 61st Annual Lindau Nobel Laureate Meeting (Lindau, Germany) (2011)
  • Outstanding Presentation Award, International Herpesvirus Workshop (Ithaca, NY) (2009)
  • Scholar Award, Achievement Rewards for College Scientists (ARCS) (2008-2011)
  • Student Athlete of the Year, Ashland University (2004)

Boards, Advisory Committees, Professional Organizations


  • Member, American Society of Pediatric Hematology/Oncology (2019 - Present)
  • Member, Children's Oncology Group (2016 - Present)
  • Member, American Society of Hematology (2016 - Present)
  • Member, American Physician Scientist Association (2005 - 2013)

Professional Education


  • Fellowship:Stanford University Pediatric Hematology Oncology Fellowship (2019) CA
  • Board Certification: Pediatrics, American Board of Pediatrics (2017)
  • Residency:University of Washington Pediatric Residency (2016) WA
  • Medical Education:Oregon Health and Sciences University Registrar (2013) OR
  • N/A, Stanford University/Lucile Packard Children's Hospital, Pediatric Hematology/Oncology (2019)
  • N/A, Seattle Children's Hospital/University of Washington, Pediatrics (2016)
  • Ph.D., Oregon Health and Science University, Molecular Microbiology and Immunology (2011)
  • M.D., Oregon Health and Science University, Medicine (2013)
  • B.S., Ashland University (Ashland, OH), Biology (2004)

Publications

All Publications


  • Multi-disciplinary evaluation of a 5-month-old with hypertrophic cardiomyopathy related to a functional adrenocortical tumor. Journal of pediatric endocrinology & metabolism : JPEM Nally, L. M., Conner, E., Paige, S., Mooney, K. L., Naber, U., Richards, R., Wright, G. 2018

    Abstract

    Background Hypertrophic cardiomyopathy (HCM) in childhood is a rare diagnosis, and associations with adrenocortical tumors (ACTs) have been rarely reported in the pediatric literature. Case Presentation We present a case of a 5-month-old who presented with HCM and during the evaluation for hypertension was found to have elevated glucocorticoids, mineralocorticoids, androgens and urine metanephrines. During preoperative evaluation, he developed shock followed by cardiogenic collapse requiring extracorporeal membrane oxygenation (ECMO); however, he did not survive. Pathology revealed an ACT with hormone production that contributed to his demise. Conclusion Adrenocortical tumors associated with hypertrophic cardiomyopathy can be life-threatening. We discuss the complex interplay of unrestricted cortical hormone production in the setting of hypertrophic cardiomyopathy that may lead to rapid decline and poor clinical outcomes.

    View details for PubMedID 30352041

  • CAR T Cell Therapy for Neuroblastoma. Frontiers in immunology Richards, R. M., Sotillo, E., Majzner, R. G. 2018; 9: 2380

    Abstract

    Patients with high risk neuroblastoma have a poor prognosis and survivors are often left with debilitating long term sequelae from treatment. Even after integration of anti-GD2 monoclonal antibody therapy into standard, upftont protocols, 5-year overall survival rates are only about 50%. The success of anti-GD2 therapy has proven that immunotherapy can be effective in neuroblastoma. Adoptive transfer of chimeric antigen receptor (CAR) T cells has the potential to build on this success. In early phase clinical trials, CAR T cell therapy for neuroblastoma has proven safe and feasible, but significant barriers to efficacy remain. These include lack of T cell persistence and potency, difficulty in target identification, and an immunosuppressive tumor microenvironment. With recent advances in CAR T cell engineering, many of these issues are being addressed in the laboratory. In this review, we summarize the clinical trials that have been completed or are underway for CAR T cell therapy in neuroblastoma, discuss the conclusions and open questions derived from these trials, and consider potential strategies to improve CAR T cell therapy for patients with neuroblastoma.

    View details for PubMedID 30459759

    View details for PubMedCentralID PMC6232778

  • Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science (New York, N.Y.) Hansen, S. G., Sacha, J. B., Hughes, C. M., Ford, J. C., Burwitz, B. J., Scholz, I., Gilbride, R. M., Lewis, M. S., Gilliam, A. N., Ventura, A. B., Malouli, D., Xu, G., Richards, R., Whizin, N., Reed, J. S., Hammond, K. B., Fischer, M., Turner, J. M., Legasse, A. W., Axthelm, M. K., Edlefsen, P. T., Nelson, J. A., Lifson, J. D., Früh, K., Picker, L. J. 2013; 340 (6135): 1237874

    Abstract

    CD8(+) T cell responses focus on a small fraction of pathogen- or vaccine-encoded peptides, and for some pathogens, these restricted recognition hierarchies limit the effectiveness of antipathogen immunity. We found that simian immunodeficiency virus (SIV) protein-expressing rhesus cytomegalovirus (RhCMV) vectors elicit SIV-specific CD8(+) T cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class II major histocompatibility complex (MHC) molecules. Induction of canonical SIV epitope-specific CD8(+) T cell responses is suppressed by the RhCMV-encoded Rh189 gene (corresponding to human CMV US11), and the promiscuous MHC class I- and class II-restricted CD8(+) T cell responses occur only in the absence of the Rh157.5, Rh157.4, and Rh157.6 (human CMV UL128, UL130, and UL131) genes. Thus, CMV vectors can be genetically programmed to achieve distinct patterns of CD8(+) T cell epitope recognition.

    View details for DOI 10.1126/science.1237874

    View details for PubMedID 23704576

    View details for PubMedCentralID PMC3816976

  • The cytoplasmic domain of rhesus cytomegalovirus Rh178 interrupts translation of major histocompatibility class I leader peptide-containing proteins prior to translocation. Journal of virology Richards, R., Scholz, I., Powers, C., Skach, W. R., Früh, K. 2011; 85 (17): 8766–76

    Abstract

    Cytomegalovirus (CMV) efficiently evades many host immune defenses and encodes a number of proteins that prevent antigen presentation by major histocompatibility complex class I (MHC-I) molecules in order to evade recognition and killing of infected cells by cytotoxic CD8(+) T cells. We recently showed that rhesus CMV-specific Rh178 intercepts MHC-I protein translation before interference of MHC-I maturation by homologues of the human CMV US6 family. Here, we demonstrate that Rh178 localizes to the membrane of the endoplasmic reticulum, displaying a short luminal and large cytosolic domain, and that the membrane-proximal cytosolic portion is essential for inhibition of MHC-I expression. We further observed that Rh178 does not require synthesis of full-length MHC-I heavy chains but is capable of inhibiting the translation of short, unstable amino-terminal fragments of MHC-I. Moreover, the transfer of amino-terminal fragments containing the MHC-I signal peptide renders recipient proteins susceptible to targeting by Rh178. The cytosolic orientation of Rh178 and its ability to target protein fragments carrying the MHC-I signal peptide are consistent with Rh178 intercepting partially translated MHC-I heavy chains after signal recognition particle-dependent transfer to the endoplasmic reticulum membrane. However, interference with MHC-I translation by Rh178 seems to occur prior to SEC61-dependent protein translocation, since inhibition of MHC-I translocation by eeyarestatin 1 resulted in a full-length degradation intermediate that can be stabilized by proteasome inhibitors. These data are consistent with Rh178 blocking protein translation of MHC-I heavy chains at a step prior to the start of translocation, thereby downregulating MHC-I at a very early stage of translation.

    View details for DOI 10.1128/JVI.05021-11

    View details for PubMedID 21715474

    View details for PubMedCentralID PMC3165821

  • Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus. Science (New York, N.Y.) Hansen, S. G., Powers, C. J., Richards, R., Ventura, A. B., Ford, J. C., Siess, D., Axthelm, M. K., Nelson, J. A., Jarvis, M. A., Picker, L. J., Früh, K. 2010; 328 (5974): 102–6

    Abstract

    Cytomegalovirus (CMV) can superinfect persistently infected hosts despite CMV-specific humoral and cellular immunity; however, how it does so remains undefined. We have demonstrated that superinfection of rhesus CMV-infected rhesus macaques (RM) requires evasion of CD8+ T cell immunity by virally encoded inhibitors of major histocompatibility complex class I (MHC-I) antigen presentation, particularly the homologs of human CMV US2, 3, 6, and 11. In contrast, MHC-I interference was dispensable for primary infection of RM, or for the establishment of a persistent secondary infection in CMV-infected RM transiently depleted of CD8+ lymphocytes. These findings demonstrate that US2-11 glycoproteins promote evasion of CD8+ T cells in vivo, thus supporting viral replication and dissemination during superinfection, a process that complicates the development of preventive CMV vaccines but that can be exploited for CMV-based vector development.

    View details for DOI 10.1126/science.1185350

    View details for PubMedID 20360110

    View details for PubMedCentralID PMC2883175

  • Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection. Proceedings of the National Academy of Sciences of the United States of America Richards, R. M., Lowy, D. R., Schiller, J. T., Day, P. M. 2006; 103 (5): 1522–27

    Abstract

    Papillomaviruses (PV) comprise a large family of nonenveloped DNA viruses that include the oncogenic PV types that are the causative agents of human cervical cancer. As is true of many animal DNA viruses, PV are taken into the cell by endocytosis and must escape from the endosomal compartment to the cytoplasm to initiate infection. Here we show that this step depends on the site-specific enzymatic cleavage of the PV minor virion protein L2 at a consensus furin recognition site. Cleavage by furin, a cell-encoded proprotein convertase, is known to be required for endosome escape by many bacterial toxins. However, to our knowledge, furin has not been previously implicated in the viral entry process. This step is potentially a target for PV inhibition.

    View details for DOI 10.1073/pnas.0508815103

    View details for PubMedID 16432208

    View details for PubMedCentralID PMC1360554

  • Stable expression of the avian retroviral oncoprotein v-Rel in avian, mouse, and dog cell lines. Virology Gilmore, T. D., Jean-Jacques, J., Richards, R., Cormier, C., Kim, J., Kalaitzidis, D. 2003; 316 (1): 9–16

    Abstract

    Overexpression of the retroviral oncoprotein v-Rel can rapidly transform and immortalize a variety of avian cells in culture. However, mammalian models for v-Rel-mediated oncogenesis have been compromised by the fact that high-level expression of v-Rel has been reported to be toxic in many mammalian cell types, including mouse 3T3 cells, Rat-1 cells, and mouse bone marrow cells. In this article, we demonstrate that 3T3 cells can support expression of v-Rel for at least 24 days when infected with a mouse stem cell virus (MSCV) retroviral vector containing v-rel. In retrovirus-infected 3T3 cells, v-Rel is located in the nucleus and can bind to DNA, but does not transform the cells. On the other hand, 3T3 and Rat-2 cells do not express v-Rel after stable transfection with a pcDNA-based v-Rel expression vector. We also show that infection of the IL3-dependent mouse B cell line BaF3 with the MSCV-v-rel vector results in expression of v-Rel, but does not convert these cells to growth factor independence. In contrast to 3T3 cells, the dog osteosarcoma D17 cell line can support a high level of v-Rel expression, after either transfection or infection with a retroviral vector. That is, v-Rel can be stably expressed as a nuclear, DNA-binding protein in D17 cells to approximately the same level as in chicken embryo fibroblasts. These results suggest that the restriction to v-Rel expression in rodent fibroblasts is generally absent in D17 cells and that the type of v-rel expression vector determines whether 3T3 cells can support stable expression of v-Rel. The findings reported here are an essential first step in the development of mammalian systems to study Rel-mediated oncogenesis.

    View details for PubMedID 14599786