OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME: Henry Hirschberg
eRA COMMONS USER NAME (credential, e.g., agency login): henrythe8
POSITION TITLE: Research Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
DEGREE
(if
applicable)
Completion
Date
MM/YYYY
City University of New York
BEE
1956-1960
Engineering
University in Oslo
MD
1969-1975
Medicine
University in Oslo
PhD
1973-1976
Immunology
Resident
1978-1984
Neurosurgery
INSTITUTION AND LOCATION
Rikshospitalet University Hospital Oslo
FIELD OF STUDY
A. Personal Statement
I have had long and varied experience in neurosurgery both in the clinic as a practicing neurosurgeon and in
medical research. I have successfully translated pre-clinical research into patient studies, and have administered
clinical protocols and many research projects (e.g. staffing, research design and goals, budget etc), in
collaboration with other clinicians, and researchers. I have produced numerous peer-reviewed publications from
each project, in all 150. Since starting out as a neurosurgical resident and all during my years as a practicing
neurosurgeon most of my research has revolved around brain tumors both in the clinic and experimentally. I
was chief of neurosurgical oncology at the University Hospital, Oslo Norway from 1990 until 2006. From 2006
I have continued my work on brain tumors exploring laser mediated light based and recently ultrasonic
therapeutic modalities at the Beckman Laser Institute at UCI and the Dept. of Health Physics UNLV Las Vegas
Nevada. The current application builds on and extends my prior work as outlined in section C.
1. Madsen SJ, Gonzales J, Nair RK, Zamora G, Berg K and Hirschberg H, Comparing the effects of light or
sonic activated drug delivery; photo/sono chemical internalization. J Environ Pathol Toxicol Oncol. 2015, in
press
2. Wang F, Zamora G, Sun CH, Trinidad A, Chun C, Kwon YJ, Berg K , Madsen SJ & Hirschberg H (2014)
Increased sensitivity of glioma cells to 5-fluorocytosine following photo-chemical internalization enhanced
nonviral transfection of the cytosine deaminase suicide gene. J Neurooncol. May; 118(1):29-37
3. Hirschberg H. Zhang MJ et al. Targeted delivery of bleomycin to the brain using photo-chemical
internalization of Clostridium perfringens epsilon prototoxin. J Neurooncol. 2009 Dec; 95(3):317
4. Madsen,SJ and Hirschberg H. (2010) Site-specific opening of the blood-brain barrier.. J Biophotonics. Jun;
3(5-6):356-67
B. Positions and Honors.
1961 Research fellow Rockland State Mental Hospital Congers New York
1962-1965 Staff scientist. Central Institute for Industrial Research Oslo Norway
1965-1969 Director of research and development. Nycotron inc. Drammen Norway
1976-1977 Internship at various hospitals in Norway
1977-1978 Visiting scientist. The Armaer Hansen Leprosy Hospital Addis Ababa Ethiopia
1978-1981 Resident Neurosurgery University Hospital Oslo Norway
1981-1982 Visiting assistant professor (immunology) Cornel medical school New York
1982-1984 Resident Neurosurgery University Hospital Oslo Norway
1986-2002 Chief executive officer Leucotech inc. Oslo Norway
1984-1990 Attending Neurosurgeon University Hospital Oslo Norway
1997-2006 Visiting researcher, The Beckman laser institute and medical clinic.
1990-2006 Consultant in Neurosurgery the University Hospital, Oslo Norway
2005-2015 Permanent chairman SPIE, biopotonics in neurosurgery
2003-present Adjunct professor. Dept. of Health Physics UNLV Las Vegas Nevada
2006-present Research Professor, The Beckman Laser Institute University of California, Irvine
Board Certification and Licensure
Medical License Boards (Norway) 1978
Neurosurgical Boards (Norway) 1984
Other Experience and Professional Memberships
1982-2006 Scandinavian Neurosurgical Society
1975-2006 The Norwegian Medical Association
1982 2006 The Norwegian Neurosurgical Society (Board member 1997-2000)
1997-2006 The Aircraft Owners and Pilots Association (AOPA) Board member 1998-2000
1995-2006 member The Scandinavian Neuro-oncology society. Board member 1999-2001
2000-2005 European Society of Photobiology member
2008-2011 Society of Neuro Oncology
2011-Present; American Association Cancer Research AACR
2015-Present; International Photodynamic Association IPA
C. Contributions to Science.
My early research, published while I was medical student, PhD candidate and neurosurgical resident, was
concerned mainly with transplantation immunology and glioma cell culture. In particular, the demonstration
of class 2 HLA antigens on human macrophages in 1976 was central to their role as antigen presenting cells.
In 1977 before starting my neurosurgical residency I spent a year at the Armaer Hansen Leprosy Hospital
Addis Ababa Ethiopia where alongside my clinical duties I pursued research on the immunology of leprosy.
We could demonstrate that it was a defect in the patient’s macrophages that lead to the immune suppression
in this devastating disease.
a. H. Hirschberg, B. Rolstad and E. Thorsby (1975) Antibody induced lymphocyte mediated damage to human
endothelial cells in vitro. Nature 255, 62.
b. H. Hirschberg, A. Kaakinen and E. Thorsby (1976) The presence of HLA-D determinants on human
macrophages. Nature 263, 63.
c. Hirschberg H., Bergh, O.J. and Thorsby, E. (1979) Clonal distribution of HLA restricted antigen-reactive T
cells in man. J. Exp. Med. 150, 1271.
d. H. Hirschberg, L. Endresen and P. Wikeby (1982) HLA antigens on glioma cells from short term cultures.
Tissue Antigens 19, 146.
e. H. Hirschberg (1984) Factors from glioma cell cultures stimulate proliferation of umbilical vein endothelial
cells in vitro. Neurophatology and Applied Neurobiology. 10, 33-42
f. H. Hirschberg (1978) The role of macrophages in the lympho proliferative response to mycobacterium
leprae in vitro. Clin.Exp. Immunol. 34, 46.
During my clinical neurosurgical career (1984-2006), and with a team of collaborators my research interest
were, brain tumor immunology, development of new neurosurgical techniques particularly neuro-navigation,
interoperative MRI, clinical studies and light based brain tumor therapy. The technique of 99mTcHexamethylpropyleneamine Oxime Leucocyte Scintigraphy we developed in 1992 for the diagnosis of brain
abscess is now standard.
a. V. Bosnes & H. Hirschberg, (1989) Immunomagnetic separation of Infiltrating T-Lymphocytes From Brain
Tumors. J. Neurosurgery 71 no. 2,, 218-24.
b. V. Bosnes, H. Hirschberg, (1988) Generation of LAK cells in vitro: Comparison of glioma patients and
normal controls. J. Neurosurgery 69: 234-238.
c. H. Hirschberg, V. Bosnes (1987). The usefulness of C reactive protein levels in the differential diagnosis of
brain abscesses. J.of Neurosurgery. 67:358-360.
d. H. Hirschberg (1989) Location of Small Subcortical Brain Tumors by a simple Skin- mounted Fuducial
Device. J. Neurosurgery 70, 280.
e. I.A.Grimstad H Hirschberg and K Rootwelt (1992) 99mTc-Hexamethylpropyleneamine Oxime Leucocyte
Scintigraphy and C-Reactive Protien Levels in the Differential Diagnosis of Brain Abscesses.
J.Neurosurgery 77: 732-736
f. H.Hirschberg (1996) Implementation Of a Stereotactic Microscope using an Optically Coupled Tracking
System. Stereotactic & Funtional Neurosurgery 66:96-101
g. H.Hirschberg, and G.Unsgaard (1997) Incorporation of Ultrasonic Imaging in an Optically Coupled
Frameless Stereotatic System. Acta Neurochirurgica 68:75-80
h. T.B. Johannesen, K.Watne, K Lote, J Norum, R. Henning, K. Tvera and H. Hirschberg (1999) Intracavity
fractionated balloon brachytherapy in glioblastoma Acta Neurchiurica 141 (2) 127-133
i. E Samset and H Hirschberg (1999) Neuro-navigation in intra-operative MRI J. Computer aided surgery
4:200-207
j. E. Samset, J.O. Høgetveit, H. Hirschberg (2005) Integrated neuro navigation system with intra-operative
image updating. J. Min. Invasive Neurosurgery, Apr; 48(2):73-76.
k. Hirschberg H, Samset E, Hole PK, and Lote K (2005) Impact of intraoperative MRI on the results of
surgery for high grade gliomas. J Minimally Invasive Neurosurgery Apr; 48(2):77-84.
l. H.Hirschberg S.Madsen, K. Lote. ,T. Chen and B.Tromberg (1999) An Indweling Balloon Catheter for
Combined Postoperative Intracavity Photodynamic and Brachytherapy J.Neuro-Oncology 44: 15-21
m. S.J Madsen, Chung-Ho Sun, B.Tromberg, and H.Hirschberg (2003) Repetitive ALA mediated
photodynamic therapy on human glioma spheroids.Jour. of Neuro-oncology 62: 243-250
n. H.Hirschberg , B.Tromberg, Chung-Ho Sun, and S Madsen (2002) ALA and ALA ester mediated
photodynamic therapy of human glioma spheroids. Jour.of neuro-oncology 2002 Mar;57(1):1-7
Despite employing the improved surgical and imaging techniques now available, combined with postoperativ
therapy such as chemo and radiotherapy, the great majority of glioma patients do suffer a recurrence of their
tumors, usually in the vicinity of the margins of the surgical resection cavity. Clearly more effective therapeutic
modalities are required. After retiring from clinical neurosurgery in 2006 my field of research has been on light
based therapy, such as photodynamic therapy (PDT) photochemical internalization (PCI) and photothermal
therapy (PTT) applied to brain tumors. Our results have demonstrated that PCI could greatly enhance
transfection rates of suppressor and suicide genes into glioma cells, and that macrophages could act as targeting
vectors for gold nanoparticles in PTT. Our most recent work has established that ultrasonic irradiation could be
an alternative to light activation for PCI, termed sonochemical internalization. This would allow treatment of
deep seated tumors.
a) H Hirschberg, E Angell-Petersen , S Spetalen ,S W Carper and , S J. Madsen: Minimally invasive
photodynamic therapy (PDT) tumor ablation of experimental rat glioma. Minim Invasive Neurosurg.
2006 Jun;49(3):135-42.
b) Madsen SJ, Angell-Petersen E, Spetalen S, Carper SW, Ziegler SA, Hirschberg H. (2006).
Photodynamic therapy of newly implanted glioma cells in the rat brain. Lasers Surg Med. 2006
Jun;38(5):540-8.
c) Hirschberg H, Uzal FA, Chighvinadze D, Zhang MJ, Peng Q, Madsen SJ. 2008 Disruption of the bloodbrain barrier following ALA-mediated photodynamic therapy. Lasers Surg Med. Oct;40(8):535-42.
d) Hirschberg H, Zhang MJ, Gach HM, Uzal FA, Chighvinadze D, Sun CH, Peng Q, Madsen SJ. (2009)
Targeted delivery of bleomycin to the brain using photo- chemical internalization of Clostridium
perfringens epsilon prototoxin. J Neurooncol. 2009 Dec;95(3):317-29. Epub 2009 Jun 9.
e) S J. Madsen, SK Baek, A R. Makkouk, T. Krasieva, and H Hirschberg (2011) Macrophages as cellbased delivery systems for nanoshells in photothermal therapy. Annals of Biomedical Engineering
(ABME) Ann Biomed Eng. 2012 Feb;40(2):507-15. Epub 2011 Oct 7.
f) Mathews MS, Shih EC, Zamora G, Sun CH, Cho SK , Kwon YJ, Hirschberg H , Glioma cell growth
inhibition following photochemical internalization enhanced nonviral PTEN gene transfection. Lasers
Surg Med. 2012 Nov; (9):746-54. Epub 2012 Sep 2
g) Steen J. Madsen, , H. Michael Gach, Qian Peng Francisco A. Uzal, , Henry Hirschberg, (2013) Increased
nanoparticle-loaded macrophage migration into the brain following PDT-induced blood-brain barrier disruption.
Lasers Surg Med. Oct;45(8):524-32.
h) Trinidad A , Hong SJ, Peng Q, Madsen SJ & Hirschberg H (2014) Combined concurrent photodynamic
and gold nanoshell loaded macrophage-mediated photothermal therapies: an in vitro study on squamous
cell head and neck carcinoma. Lasers Surg Med. 2014 Apr;46(4):310-8
i) Zamora G, Wang F, Sun CH, Trinidad A, Cho SK, Kwon YJ, Berg K , Madsen SJ & Hirschberg H
2014 Photochemical internalization mediated nonviral gene transfection: polyamine core-shell
nanoparticles as gene carrier. J Biomed Opt. 2014;19(10)
j) Steen J. Madsen, Catherine Christie, Seok Jin Hong, Anthony Trinidad, Suyog Chhetri, Qian Peng,
Francisco A. Uzal, Henry Hirschberg. 2015 Nanoparticle-loaded macrophage-mediated photothermal
therapy: potential for glioma treatment. Lasers Med Sci. 2015 Mar 21. [Epub ahead of print]
k) Madsen SJ , Gonzales J, Zamora G, Krasieva T Nair RK, and Hirschberg H. Comparing the effects of light or
sonic activated drug delivery: photo/sono chemical internalization 2016 Journal of Environmental
Pathology, Toxicology and Oncology in press.
A complete list of my publications can be found at; http://www.bli.uci.edu/profiles/profile.php?id=hhirschb
D. Research Support.
Ongoing Research Support
R21 CA179248 UC Davis (PI: L. Marcu/S. Cherry) Co.I H.
04/01/14 – 03/31/16
Hirschberg)
Photodynamic Therapy Mediated by Cerenkov Light Emitted from Radiopharmaceuticals
To develop a novel way to activate Photodynamic therapy (PDT) in vivo using an “internal” light source
produced by the Cerenkov radiation emitted by many medical radionuclides.
SE 1305
(PI: H. Hirschberg, Q. Peng)
09/01/14 – 12/30/16
The Norwegian Radium Hospital Research Foundation
Increasing the efficacy of antitumor dendritic cells (DC) glioma vaccines by photodynamic therapy (PDT)
and local injection of allogeneic glioma cells.
The specific aim of this proposal to evaluate PDT as a method to increase the efficacy of DC mediated anti
glioma immune response.
SE 1503
(PI: H Hirschberg, K. Berg)
04/01/15– 03/31/17
The Norwegian Radium Hospital Research Foundation
Photochemical internalization (PCI) enhanced nonviral transfection of pro-drug activating genes into
macrophages; a potential treatment modality for gliomas
The goal of this project is to evaluate photochemical internalization (PCI) as a method for the non-viral
transfection of the cytosine deaminase (CD) suicide gene into macrophages. The (CD) gene encodes an
enzyme that can convert the nontoxic antifungal agent, 5-fluorocytosine (5-FC), into the chemotherapeutic
drug, 5-fluorouracil (5-FU). The Ma, transfected ex vivo, will migrate to the tumor.
Completed Reasearch support (in past 3 years
SE 1106
(PI: H. Hirschberg, Q Peng)
04/01/13 – 12/30/14
The Norwegian Radium Hospital Research Foundation
Site specific blood brain barrier opening by photochemical internalization: mechanism and potentiation of
chemotherapy
The specific aim of this proposal to evaluate photochemical internalization (PCI) as a method for both the
selective and localized disruption of the blood brain barrier and the increased efficacy of chemotherapy.
UCI Cancer Center seed grant
H. Hirschberg (PI)
09/01/12 – 09/01/13
Photochemical internalization (PCI) enhanced nonviral transfection of pro-drug activating genes; a potential
treatment modality for gliomas
The goal of this project is to evaluate photochemical internalization (PCI) as a method for the non-viral
transfection of the cytosine deaminase (CD) suicide gene into gliomas cells. The (CD) gene encodes an
enzyme that can convert the nontoxic antifungal agent, 5-fluorocytosine (5-FC), into the chemotherapeutic
drug, 5-fluorouracil (5-FU).
UCI Collaborative Research Grant
H.Hirschberg (Co-I)
09/15/12 – 09/15/13
Efficient and Targeted Gene Therapy for Gliomas by Stimuli- Responsive and Photochemically Triggered
Intracellular Release of Nanomedicine
The main goal of this project is to synthesize and characterize gene carrier/DNA polyplexes together with
photosensitizer both packaged inside a polyketal shell that is designed to degrade at an endosomal pH. This
should increase the efficiency of photochemical internalization induced gene transfection while reducing the
cytotoxic effect of PDT on normal target cells.