Marlys H Witte
- Professor, Surgery
- (520) 626-6118
- Arizona Health Sciences Center, Rm. 4402J
- Tucson, AZ 85724
- lymph@surgery.arizona.edu
Biography
As Professor of Surgery and Director of Student Research, University of Arizona College of Medicine, and Secretary-General of the 42-nation International Society of Lymphology, I am engaged in extensive activities in clinical and basic lymphology – the study of lymphatics, lymph, lymphocytes, and lymph nodes in health and disease. My translational interests and contributions have spanned blood/lymphatic vascular endothelial cell biology and pathobiology in vitro and in vivo, hepatosplanchnic lymphatic/microcirculatory physiology, small animal models, in vivo lymphatic imaging, thoracic duct lymph drainage, lymphogenous cancer spread, and genomics/proteomics of lymphedema-angiodysplasia syndromes in man and experimental models, including defects, deficiency, and overexpression of human and murine lymphangio- genesis genes and their syndromic/phenotypic manifestations. Collaborative research has touched upon HIV encephalopathy, blood-brain barrier, CNS fluid dynamics, and ocular development/ disorders. I continue to work on a variety of infectious diseases and immune disorders (e.g., inflammatory bowel disease, AIDS, Kaposi sarcoma, tuberculosis, filariasis, congenital/hereditary lymphatic system syndromes, opportunistic infections/neoplasms) and direct an internationally recognized Lymphedema-Angiodysplasia clinic. Author of more than 400 peer-reviewed publications, recipient of numerous international honors and the UA College of Medicine's Gold-Headed Cane, Founders Day, and Virginia Furrow Education and Innovation Awards, I have received continuous funding from NIH (as well as other government, AMA, and non-profit agency grants) since I was a medical resident. I have also served as Program Director of UA’s only NIH General Clinical Research Center (GCRC) and am a member of the UA Arizona Comprehensive Cancer Center, Sarver Heart Center, and Viper Institute and have mentored hundreds of students supported by a continuous sequence of NIH multi-institute training grants I have acquired since 1982. These NIH research pipeline/ training grants, an earlier federally funded nationwide “Women in Medical Academia” project organized in the mid-1970's, and my service reflect a long-standing commitment to leadership training, equity, diversity, and disadvantaged populations including but not limited to underrepresented ethnic minorities, women, and the disabled. My educational activities have an overlying theme of “medical ignorance” – “what we know we don’t know, don’t know we don’t know, and think we know but don’t,” which aims to nurture “curiosity” (an “addiction” to ignorance/ unanswered questions-unquestioned answers).
Degrees
- M.D. Internal Medicine
- New York University School of Medicine, New York, New York, United States
- B.A. Zoology
- Barnard College, New York, New York, United States
Awards
- Honorary President
- Pan American Society of Lymphology, Spring 2019
- External Consultant
- Shephard University, Spring 2018
Licensure & Certification
- Diplomate, National Board of Medical Examiners (1961)
- Medical License, State of Arizona (1970)
- Certification, American Board of Internal Medicine (1967)
Interests
No activities entered.
Courses
2018-19 Courses
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Research Distinction Track
SURG 800A (Fall 2018)
2017-18 Courses
-
Research Distinction Track
SURG 800A (Fall 2017)
2016-17 Courses
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Fluid+Electrolyte Bal
SURG 850A (Spring 2017) -
Research Distinction Track
SURG 800A (Fall 2016)
Scholarly Contributions
Journals/Publications
- Erickson, R. P., Lai, L. W., Mustacich, D. J., Bernas, M. J., Kuo, P. H., & Witte, M. H. (2019). Sex-limited penetrance of lymphedema to females with CELSR1 haploinsufficiency: A second family. Clinical genetics, 96(5), 478-482.More infoA second multigeneration family with hereditary lymphedema (LE) secondary to a variant in the planar polarity gene, CELSR1, is described. Dominant inheritance of the variant was discovered using whole-exome sequencing and confirmed by Sanger sequencing. In contrast to heterozygous males, all heterozygous females showed LE during physical examination albeit variable in severity and age of onset. Lymphscintigraphy in affected females showed previously undescribed lymphatic abnormalities consistent with lymphangiectasia, valve dysfunction, and thoracic duct reflux.
- Kylathu, R., Kuo, P. H., Barber, B. J., Klewer, S. E., Bernas, M. J., Behan, S., Moedano, L., Mustacich, D., & Witte, M. H. (2019). Whole Body Lymphangioscintigraphy and SPECT-CT in Infants and Children with Lymphatic Congestion after Surgical Repair of Complex Congenital Heart Disease. 27th World Congress of Lymphology Abstract Booklet.
- Kylathu, R., Mustacich, D., Bernas, M. J., Myles, R., Kanady, J. D., Simon, A. M., Georgieva, T., Erickson, R. P., & Witte, M. H. (2019). Lymphatic Anomalies in Mice Expressing a Connexin47 Point Mutation. 27th World Congress of Lymphology Abstract Booklet.
- Kylathu, R., Witte, M. H., Barber, B. J., Dori, Y., Itkin, M., & Ghishan, F. K. (2019). Correcting protein-losing enteropathy after congenital heart disease repair by selective lymphatic embolization. Pediatr Gastroenterol Hepatol Nutr, 22(6), 1-7.
- Mahamud, M. R., Geng, X., Ho, Y. C., Cha, B., Kim, Y., Ma, J., Chen, L., Myers, G., Camper, S., Mustacich, D., Witte, M., Choi, D., Hong, Y. K., Chen, H., Varshney, G., Engel, J. D., Wang, S., Kim, T. H., Lim, K. C., & Srinivasan, R. S. (2019). GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through. Development (Cambridge, England).More infoMutations in the transcription factor GATA2 cause lymphedema. GATA2 is necessary for the development of lymphatic valves (LVs) and lymphovenous valves (LVVs), and for the patterning of lymphatic vessels. Here, we report that GATA2 is not necessary for valvular endothelial cell (VEC) differentiation. Instead, GATA2 is required for VEC maintenance and morphogenesis. GATA2 is also necessary for the expression of cell junction molecules VE-Cadherin and Claudin5 in lymphatic vessels. We identified as a target of GATA2, and embryos recapitulate the phenotypes of mice lacking GATA2. Primary human lymphatic endothelial cells (HLECs) lacking GATA2 (GATA2 ) have altered expression of Claudin5 and VE-Cadherin, and blocking activity in HLECs phenocopies these changes in expression. Importantly, overexpression of in GATA2 significantly rescues the cell junction defects. Thus, our work defines a new mechanism of GATA2 and uncovers as a novel regulator of mammalian lymphatic vascular development.
- Myles, R., Kylathu, R., Witte, M. H., Seckeler, M., & Klewer, S. E. (2019). The "Failing Fontan" Challenge to the Cardiolymphologist: Case Analysis. 27th World Congress of Lymphology Abstract Booklet.
- Paladini, D., Donarini, G., Conti, A., Constanza De Angelis, L., Witte, M. H., Genesio, R., Bernas, M., Bellini, T., Boccardo, F., Ramenghi, L. A., & Bellini, C. (2019). Early fetal hydropic changes are associated with moderate dilatation of the brain ventricular system: A clue to a possible link between cervical lymphatic engorgement and ventricular dilatation?. Lymphology, 52(1), 11-17.More infoThe aim of this study is to assess whether early cervical lymphatic obstruction is associated with a sonographically detectable dilatation of the ventricular system in the 1st trimester of pregnancy. In particular, the objective is to assess whether fetuses with non-immune hydrops fetalis (NIHF), cystic hygroma, or enlarged nuchal translucency (NT) have a greater atrial width/biparietal diameter (AW/BPD) ratio than normal at time of the combined first trimester screening scan. This retrospective study included 96 first trimester fetuses (33 normal and 63 with various degree of cervical lymphatic engorgement). Inclusion criteria were CRL in the 45-84 mm range and availability of one or more three-dimensional volume datasets of the fetal head, acquired from the BPD plane. Each three-dimensional volume dataset was opened and multiplanar correlation employed to align the three orthogonal planes. The ratio between the atrial width and the BPD (AW/BPD ratio) was used to evaluate the possible presence of increased amount of cerebrospinal fluid. Abnormal cases were placed into 4 categories: 1) enlarged non-septated NT 2.5-3.9 mm, no hydrops; 2) grossly enlarged non-septated NT / edema >3.9 mm; 3) cystic hygroma and/ or NIHF; 4) major anomalies with NT
- Sprissler, R., Bina, R., Kasoff, W., Witte, M. H., Bernas, M. J., Walter, C. M., Labiner, D. M., Lau, B., Hammer, M., & Weinand, M. E. (2019). Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy. Nature Scientific Reports.
- Witte, M. H., Bernas, M. J., Paniagua, I., Vergara, R., Roman, R., Romero, C., Bernard-Valle, M., Calderon, A., Jimenez, L., Boyer, L. V., & Alagon, A. (2019). Antivenom effect on lymphatic absorption and pharmacokinetics of Coral snake venom using large animal model. Clinical Toxicology, 57, 727-734. doi:10.1080/15563650.2018.1550199
- Bina, R. W., Kasoff, W., Sprissler, R. S., Witte, M. H., Bernas, M. J., Walter, C. M., Labiner, D. M., Hammer, M., & Weinand, M. E. (2018). Leukocyte RNA expression: Prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy. Neurosurgery, 65(1), 94.
- Dellinger, M. T., & Witte, M. H. (2018). Lymphangiogenesis, lymphatic systemomics, and cancer: Context, advances and unanswered questions. Clin. & Exp. Metastasis, 35(5-6), 419–424. doi:doi.org/10.1007/s10585-018-9907-9
- Lai, L., Erickson, R. P., Bernas, M., & Witte, M. H. (2018). From childhood onset lymphedema to fatal fetal hydrops: Possible modifying genes for a FOXC2 Mutation. Lymphology, 51(3), 85-88.
- Tanoue, N., Moedano, L., Witte, M. H., Montague, M., Lukefahr, A., & Bernas, M. (2018). Primary vs. trauma-induced Gorham Stout disease. Lymphology, 51(1), 18-27.
- Witte, M. H. (2018). Allan E. Dumont, MD, 1924-2017, Revered surgeon, teacher, and pioneering lymphologist. Lymphology. Lymphology, 51(2), 44-45.
- Woolfenden, J. M., Pak, K. Y., Witte, M. H., Gmitro, A. F., Liang, R., Banerjee, B., Patel, C., Rouse, A. R., Furenlid, L. R., Bernas, M., Cai, M., Barber, C., Gray, B. D., & Liu, Z. (2016). Characterization of TCP-1 molecular imaging probes in mouse models with xenografted human colon cancer.. J Control Release, 239, 223-230.
Presentations
- Kylathu, R., Kuo, P. H., Barber, B. J., Klewer, S. E., Bernas, M. J., Behan, S., Moedano, L., Mustacich, D., & Witte, M. H. (2019, September). Whole Body Lymphangioscintigraphy and SPECT-CT in Infants and Children with Lymphatic Congestion after Surgical Repair of Complex Congenital Heart Disease. 27th World Congress of Lymphology. Buenos Aires and Iguazu, Argentina: International Society of Lymphology.
- Kylathu, R., Mustacich, D., Bernas, M. J., Myles, R., Kanady, J. D., Simon, A. M., Georgieva, T., Erickson, R. P., & Witte, M. H. (2019, September). Lymphatic Anomalies in Mice Expressing a Connexin47 Point Mutation. 27th World Congress of Lymphology. Buenos Aires and Iguazu, Argentina: International Society of Lymphology.
- Myles, R., Kylathu, R., Witte, M. H., Seckeler, M., & Klewer, S. E. (2019, September). The "Failing Fontan" Challenge to the Cardiolymphologist: Case Analysis. 27th World Congress of Lymphology. Buenos Aires and Iguazu, Argentina: International Society of Lymphology.
Poster Presentations
- Erickson, R. P., Kylat, R., Mustacich, D. J., Bernas, M., & Witte, M. H. (2018, Fall). The phenotype of a CRISPR mouse model of a human GapJunction C2 (connexin 47) mutant causing lymphedema. ASHG 2018. San Diego, CA: American Society of Human Genetics.
Creative Productions
- Witte, M. H. (2018. TedX Bloomington Update: Marlys Witte MD. TedX BloomingtonTedX.
- Witte, M. H., Ruiz, J., Gaxiola, D., & Crown, P. (2016. Zika epidemic: Knowns! and Unknowns!. VideoNIAID.
