- Professor, Educator Scholar Track
- M.D. Medicine
- University of Arizona, Tucson, Arizona, United States
- B.A. Ecology and Evolutionary Biology
- University of Arizona, Tucson, Arizona, United States
- University of Arizona (2018 - Ongoing)
- Universtiy of Arizona, Dept of Pathology (2012 - 2018)
- University of Arizona, Tucson, Arizona (2004 - 2012)
- Good Catch Award
- BUMCT, Fall 2020
- Appreciation award from Class of 2022
- Class of 2022, College of Medicine, Spring 2020
- Dean's List for Excellence in Teaching, Year 1
- University of Arizona College of Medicine, Winter 2018
- Post-Sophomore Pathology Fellow Teaching Award
- University of Arizona Department of Pathology, Spring 2018
- Furrow Award for Excellence in Basic Science Education
- Academy of Medical Education Scholars, College of Medicine, Univ of Arizona, Fall 2015
- Academy of Medical Education ScholarsCollege of MedicineUniversity of Arizona, Fall 2014 (Award Nominee)
- Academy of Medical Education ScholarsCollege of MedicineUniversity of Arizona, Fall 2010 (Award Nominee)
- Block Appreciation Award
- Class of 2018, Foundations Block, Fall 2014
- Dean's List for Excellence in Teaching (Year II), Advanced Topics block
- College of MedicineUniversity of Arizona, Fall 2014
- College of MedicineUniversity of Arizona, Fall 2009
- John R. Davis, MD Outstanding Pathology Residency Teaching Award
- Department of PathologyCollege of MedicineUniversity of Arizona, Fall 2014
- Department of PathologyCollege of MedicineUniversity of Arizona, Fall 2008
- Department of PathologyCollege of MedicineUniversity of Arizona, Fall 2005
- Lifetime Award, Year I and II Educator of the Year
- College of MedicineUniversity of Arizona, Fall 2011
- Pride in Action Star
- University Medical Center, Winter 2010
- Furrow Award for Excellence in Innovation in Education
- Academy of Medical Education ScholarsCollege of MedicineUniversity of Arizona, Fall 2010
- Year II Outstanding Teacher in a Block, Advanced Topics
- College of Medicine University of Arizona, Fall 2010
- Year II Basic Science Educator of the Year
- College of Medicine University of Arizona, Fall 2007
- College of Medicine University of Arizona, Fall 2006
Licensure & Certification
- Hematology Pathology Board Certification, American Board of Pathology (2004)
- Anatomic and Clinical Pathology Board Certification, American Board of Pathology (2003)
No activities entered.
Clinical PathologyPATH 850B (Fall 2021)
Clinical PathologyPATH 850B (Spring 2021)
Special TopicsPATH 850C (Spring 2021)
Clinical PathologyPATH 850B (Fall 2020)
Clinical PathologyPATH 850B (Spring 2020)
Advanced TopicsMED 809 (Fall 2019)
Clinical PathologyPATH 850B (Fall 2019)
Clinical PathologyPATH 850B (Spring 2019)
Advanced TopicsMED 809 (Fall 2018)
Clinical PathologyPATH 850B (Fall 2018)
Clinical PathologyPATH 850B (Spring 2018)
Clinical PathologyPATH 850B (Fall 2017)
Clinical PathologyPATH 850B (Spring 2016)
- Russell, S. J., Duran, J., Fuchs, D., & Yeager, A. M. (2019). Atypical CD4/CD8 Lymphocytosis and Prolonged Pancytopenia Associated With Human Herpesvirus 6 Reactivation After Autologous Peripheral Blood Stem Cell Transplantation. Clinical lymphoma, myeloma & leukemia, 19(8), 531-535.
- Adams, T., Fuchs, D., Shadoan, P. K., Johnstone, L., Lau, B. M., McGhan, L., Anwer, F., & Al-Kateb, H. (2018). Unexpected favorable outcome in a patient with high grade B-cell lymphoma with abnormalities of MYC, BCL6 and BCL2 loci. Cancer genetics, 222-223, 25-31.More infoHigh grade B-cell lymphoma (HGBCL) by WHO 2016 classification requires rearrangements of MYC and BCL2 and/or BCL6, practically covering the so called "double-hit" or "triple hit" lymphomas. We report a case of HGBCL "triple-hit" lymphoma in a 64-year old female. Cytogenetic and fluorescence in situ hybridization (FISH) studies revealed complex karyotype including rearrangement of MYC to a novel, non-IG partner on chromosome 18, and rearrangement of BCL2, BCL6 and IGH as well as ins(3)(q21q27.3q25.1) among other abnormalities. FISH studies showed five copies of MYC and 3-8 copies of BCL2. Gene expression analysis by RNA sequencing showed that MYC, BCL2 and MECOM genes were overexpressed whereas BCL6 was under-expressed. BCL6 was fused to MBNL1 gene due to complex structural rearrangement. MYC was expressed in >70% of cells and BCL2 was diffusely but highly expressed by immunohistochemistry. No pathogenic mutations were identified by sequencing a 26-gene panel including TP53. The patient has unexpectedly been in complete remission for 12 months after diagnosis after intensive chemotherapy including DA-EPOCH regimen despite having HGBCL. The prognostication of HGBCL patients may further be improved by the sub-categorization of these lymphomas on the basis of more detailed genomic markers than merely the WHO 2016 classification.
- Elagib, K. E., Lu, C. H., Mosoyan, G., Khalil, S., Zasadzińska, E., Foltz, D. R., Balogh, P., Gru, A. A., Fuchs, D. A., Rimsza, L. M., Verhoeyen, E., Sansó, M., Fisher, R. P., Iancu-Rubin, C., & Goldfarb, A. N. (2017). Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition. The Journal of Clinical investigation, 127(6), 2365-2377.More infoHematopoietic transitions that accompany fetal development, such as erythroid globin chain switching, play important roles in normal physiology and disease development. In the megakaryocyte lineage, human fetal progenitors do not execute the adult morphogenesis program of enlargement, polyploidization, and proplatelet formation. Although these defects decline with gestational stage, they remain sufficiently severe at birth to predispose newborns to thrombocytopenia. These defects may also contribute to inferior platelet recovery after cord blood stem cell transplantation and may underlie inefficient platelet production by megakaryocytes derived from pluripotent stem cells. In this study, comparison of neonatal versus adult human progenitors has identified a blockade in the specialized positive transcription elongation factor b (P-TEFb) activation mechanism that is known to drive adult megakaryocyte morphogenesis. This blockade resulted from neonatal-specific expression of an oncofetal RNA-binding protein, IGF2BP3, which prevented the destabilization of the nuclear RNA 7SK, a process normally associated with adult megakaryocytic P-TEFb activation. Knockdown of IGF2BP3 sufficed to confer both phenotypic and molecular features of adult-type cells on neonatal megakaryocytes. Pharmacologic inhibition of IGF2BP3 expression via bromodomain and extraterminal domain (BET) inhibition also elicited adult features in neonatal megakaryocytes. These results identify IGF2BP3 as a human ontogenic master switch that restricts megakaryocyte development by modulating a lineage-specific P-TEFb activation mechanism, revealing potential strategies toward enhancing platelet production.
- Duncan, J., Chen, Y., Fuchs, D., Cantu, C., & Wang, M. (2016). Follicular Lymphoma Presenting Solely as Chronic Follicular Conjunctivitis. Cornea, 35(3), 395-8.More infoConjunctival lymphoma rarely can have atypical clinical presentations. The authors report a case of conjunctival follicular lymphoma that presented solely as bilateral chronic follicular conjunctivitis. This case underscores that the pathological characteristics of conjunctival follicles can only be determined by histopathologic examination.
- Taverna, J., Nair, A., Yun, S., Paulson, S., Schatz, J. H., Persky, D., Fuchs, D., & Puvvada, S. (2014). A rare presentation of in situ mantle cell lymphoma and follicular lymphoma: a case report and review of the literature. Case reports in hematology, 2014, 145129.More infoA 65-year-old gentleman presented with left groin swelling over the course of two months. Physical exam revealed nontender left inguinal adenopathy, and computed tomography scans detected multiple lymph nodes in the mesenteric, aortocaval, and right common iliac regions. An excisional lymph node biopsy was performed. Pathologic evaluation demonstrated follicular center site which stained positive for PAX5, CD20, CD10, Bcl-2, Bcl-6, and mantle zone cells. These findings demonstrated CCND1 and CD5 positivity, suggesting composite lymphoma comprising follicular lymphoma (FL) with in situ mantle cell lymphoma (MCLIS). FL is known as indolent non-Hodgkin lymphoma; however, the clinical significance of a coexisting MCLIS continues to be elusive, and optimal management of these patients remains largely unknown. This case illustrates the diagnostic and therapeutic challenges of composite lymphomas. This paper also discusses advances in molecular pathogenesis and lymphoma genomics which offer novel insights into these rare diseases.
- Gorlitsky, B. R., Zangeneh, T., Fuchs, D., & Cox, C. (2013). Fifty, febrile, and fatigued: high ferritin as a clue in diagnosis. The American journal of medicine, 126(11), e3-4.
- Fuchs, D. A., McGinn, S. G., Cantu, C. L., Klein, R. R., Sola-Visner, M. C., & Rimsza, L. M. (2012). Developmental differences in megakaryocyte size in infants and children. American journal of clinical pathology, 138(1), 140-5.More infoDevelopmental differences in megakaryocytes between neonates and adults have been described. However, the age at which megakaryocytes make a transition to an adult phenotype is unknown. Small megakaryocytes are often described as "dysplastic" in the pathology literature. Thus, recognizing the normal features of megakaryocytes at different ages has diagnostic implications. We identified 72 samples from 61 patients, aged 3 days to 80 years, who had negative staging based on bone marrow examination. Megakaryocyte diameters, as highlighted with anti-CD61, were measured. A scatter plot of megakaryocyte size by age revealed a normal distribution of sizes at the youngest ages, with a shift to multiple peaks starting at 24 months indicating that neonates have megakaryocytes of uniform sizes, which diverge into separate clusters of smaller and larger cells beginning at 2 years; this is followed by an overall shift toward larger megakaryocytes at age 4 years. These observations have direct implications for the evaluation of bone marrow megakaryocytes in young children.
- Bartley, A. N., Nelson, C. L., Nelson, D. H., & Fuchs, D. A. (2007). Disseminated extramedullary myeloid tumor of the gallbladder without involvement of the bone marrow. American journal of hematology, 82(1), 65-8.More infoExtramedullary myeloid tumors (myeloid sarcomas) are rare neoplasms that are composed of myeloid precursors. They usually arise concurrently with a diagnosis of acute myeloid leukemia, chronic myeloid leukemia, or other myeloproliferative disorders. They may also indicate relapsing disease in a patient with a prior history of leukemia or myeloproliferative disorder. We present our findings of a 63-year-old female diagnosed with extramedullary myeloid tumor first presenting in the gallbladder. She subsequently developed respiratory failure; pre- and postmortem bone marrow studies were negative for leukemia by morphology, flow cytometry, and karyotypic analysis. However, the myeloid neoplasm was disseminated throughout most of her remaining organs. Immunohistochemical stains of the cells indicated a neoplasm of myelomonocytic derivation (CD4, CD43, CD45, CD68, myeloperoxidase, and lysozyme positive). To our knowledge, this is the first report of an extramedullary myeloid neoplasm of the gallbladder with disseminated disease without involvement of the bone marrow.
- Cohen-Barak, O., Erickson, D. T., Badowski, M. S., Fuchs, D. A., Klassen, C. L., Harris, D. T., & Brilliant, M. H. (2007). Stem cell transplantation demonstrates that Sox6 represses epsilon y globin expression in definitive erythropoiesis of adult mice. Experimental hematology, 35(3), 358-67.More infoSox6, a member of the Sox transcription factor family, is essential for the silencing of epsilon y globin gene expression in definitive erythropoiesis of mice. Homozygous Sox6-null mice are neonatally lethal, precluding analysis at later stages. We created adult mice that are deficient in Sox6 specifically in hematopoietic tissues by transplanting embryonic liver stem cells from Sox6-deficient mice into lethally irradiated congenic wild-type adult mice. The mice receiving mutant stem cells (mutant engrafted) showed high expression levels of epsilon y in bone marrow, spleen, and circulating blood compared with mice receiving wild-type and heterozygous stem cells (control engrafted). The level of expression of epsilon y in circulating blood was directly correlated with the percentage of successful mutant donor cell engraftment. Additionally, the mutant engrafted adult mice showed an increase in erythroid precursor cells in bone marrow, spleen, and blood. Thus, Sox6 continues to function as a major regulator of epsilon y in adult definitive erythropoiesis and is required for normal erythrocyte maturation. Therefore, Sox6 may provide a novel therapeutic target by reactivating epsilon y in patients with hemoglobinopathies such as sickle cell anemia and beta-thalassemia.
- Ignatz, M., Sola-Visner, M., Rimsza, L. M., Fuchs, D., Shuster, J. J., Li, X., Jotwani, A., Staba, S., Wingard, J. R., Hu, Z., & Slayton, W. B. (2007). Umbilical cord blood produces small megakaryocytes after transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 13(2), 145-50.More infoDelayed platelet engraftment is a major complication of umbilical cord blood (CB) transplantation. Megakaryocytes derived from CB in vitro are smaller than megakaryocytes derived from bone marrow (BM) or mobilized peripheral blood from adults. Small megakaryocyte size may contribute to delayed platelet engraftment. To test whether small size persists after transplantation, we measured megakaryocyte size, concentration, and maturational stage in BM biopsy specimens obtained after transplantation in archived BM samples from patients receiving CB (CB group, n = 10) versus mobilized peripheral blood or BM transplantation (BM group, n = 9). Megakaryocytes in the postengraftment BM samples were significantly smaller in the CB group than in the BM group (median diameter, 16.7 vs 22.0 microm). There were no significant differences in megakaryocyte concentration or maturational stage between the CB and BM groups. For the first time, we demonstrate that the attainment of adult size in CB-derived megakaryocytes is delayed after human CB transplantation.
- Rimsza, L. M., Farinha, P., Fuchs, D. A., Masoudi, H., Connors, J. M., & Gascoyne, R. D. (2007). HLA-DR protein status predicts survival in patients with diffuse large B-cell lymphoma treated on the MACOP-B chemotherapy regimen. Leukemia & lymphoma, 48(3), 542-6.More infoLoss of major histocompatibility class II (MHC class II) molecules on diffuse large B-cell lymphoma (DLBCL) has been associated with poor survival; however, none of these reports analysed a uniformly treated patient cohort. This study was designed to validate one MHC class II antigen, HLA-DR, as a prognostic marker in patients uniformly treated with the MACOP-B regimen. Immunostaining results were correlated with the international prognostic index (IPI) score and overall survival (OS). Of the 97 cases, 82 had interpretable staining. Of these, 52 expressed HLA-DR (median OS, 16.2 years) while 30 were negative (median OS, 4.2 years, P = 0.037). The IPI was also predictive of OS in the study group (P = 0.023). A Cox multivariate model established both IPI (P = 0.031) and HLA-DR (P = 0.04) as independent predictors of OS. This is the first demonstration of the prognostic relevance of HLA-DR in a uniformly treated DLBCL patient group.
- Mahadevan, D., DiMento, J., Croce, K. D., Riley, C., George, B., Fuchs, D., Mathews, T., Wilson, C., & Lobell, M. (2006). Transcriptosome and serum cytokine profiling of an atypical case of myelodysplastic syndrome with progression to acute myelogenous leukemia. American journal of hematology, 81(10), 779-86.More infoA Native American-Indian female presenting with anemia and thrombocytosis was diagnosed with myelodysplastic syndrome (MDS, refractory anemia). Over the course of 5 years she developed cytopenias and periods of leukocytosis with normal bone marrow (BM) blast counts, features of an unclassifiable MDS/MPS syndrome. The patient ultimately progressed to acute myelogenous leukemia (AML, FAB M2) and had a normal karyotype throughout her course. The episodes of leukocytosis were associated with infectious complications. Transformation to AML was characterized by a BM blast percentage of 49%. Peripheral blood and BM samples were obtained for serum protein analysis and gene expression profiling (GEP) to elucidate her disease process. An ELISA assay of the serum analyzed approximately 80 cytokines, which demonstrated that hepatocyte growth factor/scatter factor and insulin-like growth factor binding protein 1 were markedly elevated compared to normal. GEP demonstrated a unique "tumor molecular profile," which included overexpression of oncogenes (HOXA9, N-MYC, KOC1), proliferative genes (PAWR, DLG5, AKR1C3), invasion/metastatic genes (FN1, N-CAM-1, ITGB5), pro-angiogenesis genes (c-Kit), and down regulation of tumor suppressor genes (SUI1, BARD1) and anti-apoptotic genes (PGLYRP, SERPINB2, MPO). Hence, a biomics approach has provided insight into elucidating disease mechanisms, molecular prognostic factors, and discovery of novel targets for therapeutic intervention.
- Yi, Z., Cohen-Barak, O., Hagiwara, N., Kingsley, P. D., Fuchs, D. A., Erickson, D. T., Epner, E. M., Palis, J., & Brilliant, M. H. (2006). Sox6 directly silences epsilon globin expression in definitive erythropoiesis. PLoS genetics, 2(2), e14.More infoSox6 is a member of the Sox transcription factor family that is defined by the conserved high mobility group (HMG) DNA binding domain, first described in the testis determining gene, Sry. Previous studies have suggested that Sox6 plays a role in the development of the central nervous system, cartilage, and muscle. In the Sox6-deficient mouse, p100H, epsilony globin is persistently expressed, and increased numbers of nucleated red cells are present in the fetal circulation. Transfection assays in GM979 (erythroleukemic) cells define a 36-base pair region of the epsilony proximal promoter that is critical for Sox6 mediated repression. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrate that Sox6 acts as a repressor by directly binding to the epsilony promoter. The normal expression of Sox6 in wild-type fetal liver and the ectopic expression of epsilony in p100H homozygous fetal liver demonstrate that Sox6 functions in definitive erythropoiesis. The present study shows that Sox6 is required for silencing of epsilony globin in definitive erythropoiesis and suggests a role for Sox6 in erythroid cell maturation. Thus, Sox6 regulation of epsilony globin might provide a novel therapeutical target in the treatment of hemoglobinopathies such as sickle cell anemia and thalassemia.
- List, A., Kurtin, S., Roe, D. J., Buresh, A., Mahadevan, D., Fuchs, D., Rimsza, L., Heaton, R., Knight, R., & Zeldis, J. B. (2005). Efficacy of lenalidomide in myelodysplastic syndromes. The New England journal of medicine, 352(6), 549-57.More infoIneffective erythropoiesis is the hallmark of myelodysplastic syndromes. Management of the anemia caused by ineffective erythropoiesis is difficult. In patients with myelodysplastic syndromes and symptomatic anemia, we evaluated the safety and hematologic activity of lenalidomide, a novel analogue of thalidomide.
- Rimsza, L. M., Roberts, R. A., Miller, T. P., Unger, J. M., LeBlanc, M., Braziel, R. M., Weisenberger, D. D., Chan, W. C., Muller-Hermelink, H. K., Jaffe, E. S., Gascoyne, R. D., Campo, E., Fuchs, D. A., Spier, C. M., Fisher, R. I., Delabie, J., Rosenwald, A., Staudt, L. M., & Grogan, T. M. (2004). Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. Blood, 103(11), 4251-8.More infoThe Leukemia and Lymphoma Molecular Profiling Project recently published results from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four gene expression "signatures" were identified as correlated with patient outcome, including the major histocompatibility complex (MHC) class II genes (eg, HLA-DRA) which correlated with better survival. We further analyzed the effects of HLA-DRA on survival and correlated gene expression with protein status and tumor-infiltrating lymphocytes. The 5-year overall survival was 24% in the lowest 10% of HLA-DRA expression, 37% in the 10% to 25% group, 50% in the 25% to 50% group, and 55% for patients in the highest 50%. Further analysis demonstrated that the hazard ratio of death was a nonlinear function of HLA-DRA expression. Adjustment for the International Prognostic Index did not alter the impact of HLA-DRA on survival. Other MHC class II genes were found to predict survival similarly. Microarray HLA-DRA expression correlated with the presence or absence of human leukocyte antigen-DR (HLA-DR) protein in 20 of 22 cases assessed. Fewer tumor-infiltrating CD8(+) T cells were detected in MHC class II-negative cases compared with positive cases (2.8% versus 11.0%; P =.001), supporting the hypothesis that loss of tumor immunosurveillance has a devastating effect on patient outcome in DLBCL.
- Sola, M. C., Slayton, W. B., Rimsza, L. M., Perez, J. A., Fuchs, D., Fuch, D., Calhoun, D. A., & Christensen, R. D. (2004). A neonate with severe thrombocytopenia and radio-ulnar synostosis. Journal of perinatology : official journal of the California Perinatal Association, 24(8), 528-30.More infoBone marrow failure syndromes can be associated with abnormalities of the forearms. We observed a neonate with congenital thrombocytopenia who had bilateral radio-ulnar synostosis and fifth finger clinodactly. We performed an evaluation of the mechanism causing the thrombocytopenia using a combination of direct and indirect measures of thrombopoiesis. These tests indicated decreased platelet production. This entity of congenital hyporegenerative thrombocytopenia with bilateral radio-ulnar synostosis and fifth-finger clinodactly is an uncommon but easily recognizable form of congenital amegakaryocytic thrombocytopenia (CAMT). This entity can be distinguished from the TAR syndrome (thrombocytopenia and absent radii) by the distinctive orthopedic issues, different underlying genetic mutations, and a more worrisome prognosis for CAMT than for TAR.
- Al-kateb, H., Fuchs, D., & Anwer, F. (2017, March). High Grade B-cell Lymphoma with Rearranged MYC to an Unknown Partner on Chromosome 18". American College of Medical Genets and Genomics, Annual Clinical Genetics Meeting. Phoenix, AZ.
- Duran, J., & Fuchs, D. (2017. Macrothrombocytopenia and neutrophils with Döhle-like bodies(pp #00061179).