Medical College of Wisconsin
Medical College of Wisconsin Medical College of Wisconsin
Research Bench Lab
Microbiology & Immunology
Sieber_Fritz

Fritz Sieber, PhD

Professor (with tenure), Pediatrics (Hematology/Oncology/BMT) and Microbiology & Immunology

Locations

  • Microbiology & Immunology

Contact Information

General Interests

Selenium-based Experimental Therapeutics

Education

PhD, (Dr sc nat ETH ), Cell Biology/Biochemistry, Swiss Federal Institute of Technology, Zurich, 1976
MS, (Dipl Natw ETH ), Developmental Biology/Biochemistry, Swiss Federal Institute of Technology, Zurich, 1971

Biography

Chair, Steering Committee, CRI Postdoctoral Training Program

Research Experience

  • Amifostine
  • anti-cancer agents
  • Antimalarials
  • Antineoplastic Agents, Alkylating
  • Bone Marrow Purging
  • Bone Marrow Transplantation
  • Cell Line, Transformed
  • Cell Line, Tumor
  • clonal assay
  • cytotoxic photoproducts
  • cytotoxic subnano selenium
  • experimental therapeutics

Clinical Expertise

  • autologous hematopoietic stem cell transplantation
  • ex vivo purging
  • photochemical purging

Research Interests

Research Description

1) Development of second-generation merocyanine photosensitizers with improved antineoplastic, antiviral, and anti-protozoan activities. Of particular interest are selone analogs that are characterized by extremely high singlet oxygen quantum yields and the photochemical generation of cytotoxic photoproducts. One merocyanine-based application has made the transition from bench to clinic and is showing promising results in a phase I/II trial in adult patients with high-risk acute myelogenous leukemia.

2) Proteinated subnanoparticles of elemental selenium as a novel class of anti-cancer agents. When selenomerocyanine dyes are exposed to light in the presence of oxygen, they generate subnanoparticles of elemental selenium that combine with serum albumin or lipoproteins to form conjugates that are highly cytotoxic to tumor cells but well tolerated by normal cells. A 1-hour exposure to micromolar concentrations of proteinated selenium is sufficient to reduce clonogenic tumor cells by ≥5 orders of magnitude while preserving virtually all normal pluripotent hematopoietic stem cells.

sieber_figure1

Figure 1: Photochemical generation of proteinated subnanoparticles of elemental selenium and their effects on leukemia and normal hematopoietic stem cells. The protein component acts as a Trojan horse that exploits the enhanced capacity of tumor cells to bind and internalize serum albumin and lipoproteins. The cytotoxic entity (elemental selenium) is preferentially delivered to tumor cells as part of a physiological process.

3) High-dose selenium for the mitigation of therapy-induced toxicities. This project grew out of an effort to develop medical countermeasures against radiation injuries caused by nuclear accidents or acts of radiological terrorism. We could show that very high (supranutritional) doses of dietary selenium are surprisingly effective at reducing radiation injury to kidney, liver, heart, and lung even if the intervention is initiated after radiation exposure. We are now in the process of extending this approach to the mitigation of therapy-induced toxicities in animal models of radiation- and chemotherapy.

Publications

Publications of Fritz Sieber PhD from the Faculty Collaboration Database