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WELCOME TO ANTON'S HOMEPAGE
I hope things don't go downhill from here...


This webpage presents my CV in a graphical link-rich form, for your browsing pleasure...it's a bit slow loading, but if you can wait..

Välg stiget osäkert lovande smärtsam och du har valt rätt.
Biology and Medicine on the Banks of the Mississippi
I was born and raised in south Minneapolis, a conurbation of 2 million citizens straddling the Mississippi River halfway between the equator and the north pole. I grew up close to the shore of one of 29 lakes within the City of Minneapolis, created by the retreat of the last glaciers in the late Pleistocene. The lake is named Lake Harriet, in honor of the wife of Colonel Leavenworth, who himself is honored (?) in the name of a renowned federal prison in Kansas. The Colonel and wife actually lived in the area in the early part of the nineteenth century, when the Colonel was stationed at a frontier outpost called Fort Snelling, built on a bluff at the confluence of the Minnesota and Mississippi Rivers. I taught geology there to gradeschool kids while I was a high school student in the Minneapolis Public Schools, hotbed of progressive and liberal thinking.

Users of Mac/OS may download the haunting sound from off a Minnesota lake here.

My university education was also at a public institution, the University of Minnesota, which like Minneapolis itself, also straddles the Mississippi River, not far downstream from the Falls of St. Anthony, which provided energy to the saw- and flour- mills forming the early economic mainstay of the city. During my three years at the U of M, it was headed by an intelligent Republican (not necessarily an oxymoron!) named Malcolm Moos, who wrote President Eisenhower's well-quoted speech warning of the development of a military-industrial complex. During the mid-1970s, under the Moos presidency, the U of M provided fertile ground for hot new ideas and technologies in biology and medicine, which helped turn my intellectual interest into these areas. For example, the University of Minnesota Hospitals provided training for Drs. Norman Shumway and Christian Barnard, pioneers in heart transplantation and open heart surgery. Bone marrow transplantation (1968) and kidney transplantation (1974) was pioneered at U of M Hospitals in the late 1960s and early 1970s, thanks to developments in surgery and immunogenetics (human HLA Class II antigens were first described there in 1977).
HLA Class I molecule bearing processed Ag

Under the leadership of John S. Najarian, M.D., U of M Hospitals became the mecca for organ transplantation in the 1970s, focusing first on kidney, which accounted for several thousand operations per year by the end of the decade. My first exposure to biology was provided in a beginning course taught by a cell biologist (Robert G. McKinnell) and an ecologist ( Eville Gorham, now a member of the National Academy of Sciences (NAS), who first described how the A-bomb fallout product radioactive Sr became concentrated in lichens and moss, and from there entering into reindeer). McKinnell was one of the pioneers in the technique of nuclear transplantation, enabling the test of fundamental concepts in genetics and developmental biology.

THE PURPOSE OF EDUCATION IS NOT TO FILL AN EMPTY MIND, BUT TO OPEN A CLOSED ONE

Fiat Lux: Light in the West
There's a feeling I get when I look to the west
And my spirit is crying for leaving
--"Stairway to Heaven" by Robert Plant
From there I went west to Berkeley, where I attended graduate school at the University of California, writing a Ph.D. dissertation in the lab of Fred H. Wilt on The Control of Histone Gene Expression During Early Sea Urchin Development, realizing the early influences I picked up at the U of M. My thesis committee was an odd assemblage of scientists whose only connection was an interest in developmental biology, including Daniel Mazia (who first isolated the mitotic apparatus in the 1950s from cleavage-stage sea urchin embryos) and John Gerhart (who as a graduate student with Art Pardee in the early 1960s demonstrated regulatory and catalytic subunits of aspartyl transcarbamylase (ATCase), fulfilling predictions of allosteric control put forward by Jacob and Monod). Both are now members of the NAS. The youngest member of my committee was G. Steven Martin, a new faculty member at Berkeley studying the role of the transforming protein Src in the developmental switch between proliferation and differentiation. Using mutants of Rous Sarcoma Virus (RSV) temperature-sensitive for transformation, Steve and his postdoc Kathy Radke demonstrated phosphorylation at the permissive temperature (35oC) of a 60 kD protein which turned out to be pp60 Src, a protein which provided a biochemical explanation of neoplastic transformation. Another postdoc in Steve's lab, Tony Pawson, moved the focus of Src to phosphotyrosine, a modified amino acid first described in 1979 by Tony Hunter at the Salk Institute. Hunter described a region in the pp60 Src protein known as the Src-homology domain 2, now simply known as SH2, which folds into a pocket in Src (and other proteins from Hydra to Homo) capable of binding phosphotyrosine.SH2 domain
I stayed on at Berkeley for a short time after finishing my Ph.D. to work with a Mazia postdoc named Peter G. Meyerhof (grandson of the Nobel laureate) to understand the biochemistry of a poorly- understand phenomenon called cytostatic factor (CSF), which when injected into one of the two blastomeres of the frog Xenopus at the two-cell stage, would arrest all future cleavage on the injected side. Peter and I did not get far in this project, but had we consulted the crystal ball, we would have seen that like Src, the CSF story also involve protein kinases, as Jim Maller later showed for maturation-promotion factor (MPF), another Xenopus factor first described by Yoshio Masui and his colleagues at the University of Toronto. But what I did not know in 1980 was that the CSF story would involve great "RSKs", the name for a family of S/T kinases which would mediate diverse events in signaling the onset of meiosis in frogs, cell survival in neurons (RSK-2, the gene defective in the Coffin-Lowry Syndrome) and in skeletal muscle differentiation. I had a great time at Berkeley, and spend alot of time up in Strawberry Canyon, or up in the hills behind Bowles Hall and the Greek Theatre, thinking great thoughts, like those inspired by viewing the photographs of Ansel Adams (see photo above left) from his 1968 book "Fiat Lux").

Peptide Growth Factors, Receptors and Oncogenes under the Midnight Sun
Swedish flagMora, Sweden
After finishing my Ph.D. I moved to Sweden in 1982, soon after the elderly President Reagan proved himself teflon by his rapid recovery from a would-be assassin's bullet. The impetus behind my emigration had much to do with a poster I picked up in th early 1970s in San Francisco depicting Nixon, Agnew and Reagan as the three monkeys Hear-No-Evil, See-No-Evil, Speak-No-Evil. I spent three years at the University of Umeå in Sweden, at the southern edge of Lapland, about as far from the teflon monkey as I could imagine.
This was a town where the median age was 14, and a young group of energetic Swedes were set to make a name for themselves (probably so they could get better jobs farther south!). There I linked up with a young guest professor Rolf Ohlsson and his wife Susan Pfeifer, to look at oncogenes and growth factors in the control of cell division in early human development and placentation. I became a part of a team that included a human geneticist (Gö sta Holmgren) and a gynecologist (Jan Rydnert). We managed to publish two papers in Cell and one in PNAS before we all left for more southerly climes (Stockholm and Minnesota).
Swedish cabins in falu rö d
The work made a big splash at the time, thanks to the newly-established linked between neoplastic transformation and the growth factor PDGF, whose B chain is encoded in the c-sis oncogene. This link was provided by two independent groups in June 1983, one Swedish-British collaboration (publishing in Nature) and one American collaboration (publishing in Science). Like the earlier understanding of Src as a tyrosine kinase, the definition of Sis as PDGF was a shot-in-the-arm for a newly-emerging field of signal transduction, which today smothers cancer, biochemistry, cell biology, and embryology like a shroud of details. Compared to today, life was much simpler in 1985, when we collaborated with Bengt Westermark and Calle Heldin at the University of Uppsala to show how the PDGF-myc axis could provide an autocrine or paracrine loop controlling cell proliferation in the early human placenta: Cell 41, 301-312 (1985).

TGFs in the Cornfields of Southern MInnesota and PDGF in the Hub of the Universe
From there I moved back to the Land of the Free and the Home of the Brave, settling in with Hal Moses (photo at left) at the Mayo Clinic to study a protein called transforming growth factor type beta (TGFß). My project was to clone the cDNA for TGFß based on rudimentary amino acid sequence Hal had obtained from his extremely pure human TGFß. We were beaten by a Genentech group headed by Rik Derynck, so I turned my attention to another growth factor related only by name--transforming growth factor alpha (TGFa). There at Mayo, I got together with a gastroenterologist working in the Moses lab, Robert J. Coffey, Jr., to look at the role of TGFa in colonic neoplasia. As a control for a Northern blot, prepared RNA from a culture of human epidermal keratinocytes grown by a dermatologist, Mark Pittelkow. Bob and I expected this RNA to provide a negative control for TGFa expression, and were certain that we had mislabeled the blot when we first saw the whopping signal in the keratinocyte lane. After finding that this transforming growth factor was expressed in cultured human keratinocytes, I went to the nursery at Mayo to collect seven penis foreskins to see whether TGFa expression was an artifact of culture or a representation of something real. It turned out that normal human (fore) skin expressed the TGFa gene to a low degree and also made the protein product, which resulted in a Nature paper in 1987 co-authored with Derynck and one of his Genentech group.
After Moses left Mayo to convert a rather moribund Department of Anatomy at Vanderbilt University School of Medicine into a dynamic Department of Cell Biology and Anatomy, I headed east to Boston, to join the Center for Blood Research in close association with Harry Antoniades. Harry was a biochemist who first described insulin-like growth factor I (IGF-I) as "bound insulin" in 1956, and had abandoned his attempts to purify IGF-I from serum when he found an even more potent mitogen called platelet-derived growth factor (PDGF). Harry and Heldin truly "pushed the envelope" on PDGF in the late 1970s-early 1980s, purifying PDGF to homogeneity. Harry provided the first peptide sequence from PDGF in May 1983, showing in fact two N-termini defining two related by distinct chains, which he called A and B.
What I learned best under Harry's mentorship was how to write an NIH grant. I attempted my first NIH grant submission in October 1986, as an Instructor in the Department of Pediatrics at Harvard Medical School. The proposal focused on understanding the structure of PDGF. In that first NIH proposal, I spent half a page describing a new technique called polymerase chain reaction (PCR), which was executed at that time MANUALLY moving tubes through a series of waterbaths, adding extra Klenow at each cycle. The proposal used PCR to generate chimeric cDNA constructs using the PDGF B chain cDNA and the newly-closed PDGF A chain cDNA as template. One of the most interesting people I met at CBR was Edmond J. Yunis who was interested in the relationship between aging and the immune system.
When the Center hired a new President, they needed lab space to recruit Tim Springer, so they forced me to move into Harry's lab or else leave. In response, I moved my lab in with Antoniades and began looking at the expression of PDGF receptor in blood cells, in collaboration with Panagiotis ("Takis") Pantazis . The deal was a raw one for me, but a sweet one for the Center; they made Tim a named professor at Harvard Med, and despite a bumpy history, Tim garnered enough votes this spring to win election to the NAS.
...After a few cramped months in 1988, out I got!
Moving to Michigan:
"SI QVAERIS PENINSULAM AMOENAM CIRCUMSPICE (If you seek a pleasant peninsula, look about you)

Center for Molecular Biology in Motown
In January 1989, I was recruited to the Center for Molecular Biology at Wayne State University in Detroit, a sprawling urban university in the midst of a moribund metropolis. Thanks to visionary leadership from its President (David Adamany) and the retirement of Coleman ("Krugerrand") Young as Mayor of Detroit, both the city and the University (with its urban mission are beginning a remarkable metamorphosis. The Center for Molecular Biology began its life in 1987 as a Center for Research Excellence, an offshoot of the Michigan Strategic Fund (MSF). MSF was the brainchild of Jamie Kenworthy, a bright and creative politician in the Michigan Department of Commerce. Like his mentor, then-Governor James Blanchard, Kenworthy saw light at the end of the tunnel for the race riot-scarred city in a Rust Belt state. Their answer was economic diversification, to get the state off its addiction to the automotive economy. Molecular Biology in Motown was one way to pump some new blood into the ailing region.

The University's Center for Molecular Biology and its Department of Molecular Biology were formally merged into one unit in October 1994, to create an organized research unit, the Center for Molecular Medicine and Genetics. The question, What is molecular medicine...
Protein tyrosine kinases.

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